IL 6 is a pro-inflammatory cytokine involved in driving inflammation and the acute phase immune response. Hence, it is important to predict SNPs which could affect IL-6 stability and thus inflammatory conditions. Therefore, this study was undertaken to find the functional nsSNPs in IL 6. Out of total 243 SNPs, 37 were nsSNPs (non-synonymous), 7 occurred in the mRNA 3’UTR, 7 occurred in 5’ UTR region, 193 occurred in intronic regions and rest were other types of SNPs. Among the predicted nsSNPs, rs2069860, rs11544633 were identified as deleterious and damaging by different programs. Additionally, I-Mutant showed a decrease in stability for these nsSNPs upon mutation. Protein structural analysis with these amino acid variants was performed by using I-Mutant and Swiss PDB viewer to check their molecular dynamics and energy minimization calculations. We also identified several IL 6 sites that may undergo post-translational modification, including sites that coincide with the location of high-risk nsSNPs. This study suggested that D162V and P119L variants of IL 6 could directly or indirectly destabilize the amino acid interactions and could be useful for evaluation of genotype association study with inflammatory diseases.
{"title":"Computational analysis to identify deleterious nsSNPs and its impact on IL 6 protein in inflammation","authors":"B. Dabhi, K. Mistry","doi":"10.14800/ICS.777","DOIUrl":"https://doi.org/10.14800/ICS.777","url":null,"abstract":"IL 6 is a pro-inflammatory cytokine involved in driving inflammation and the acute phase immune response. Hence, it is important to predict SNPs which could affect IL-6 stability and thus inflammatory conditions. Therefore, this study was undertaken to find the functional nsSNPs in IL 6. Out of total 243 SNPs, 37 were nsSNPs (non-synonymous), 7 occurred in the mRNA 3’UTR, 7 occurred in 5’ UTR region, 193 occurred in intronic regions and rest were other types of SNPs. Among the predicted nsSNPs, rs2069860, rs11544633 were identified as deleterious and damaging by different programs. Additionally, I-Mutant showed a decrease in stability for these nsSNPs upon mutation. Protein structural analysis with these amino acid variants was performed by using I-Mutant and Swiss PDB viewer to check their molecular dynamics and energy minimization calculations. We also identified several IL 6 sites that may undergo post-translational modification, including sites that coincide with the location of high-risk nsSNPs. This study suggested that D162V and P119L variants of IL 6 could directly or indirectly destabilize the amino acid interactions and could be useful for evaluation of genotype association study with inflammatory diseases.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74229295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Invariant natural killer T (iNKT) cells are a distinct lineage of αβ T lymphocytes with the capacity to recognize glycolipid antigens in the context of the atypical major histocompatibility complex (MHC) class I molecule CD1d. In response to engagement of the T cell receptor (TCR), iNKT cells efficiently and rapidly produce a broad range of cytokines and several chemokines. iNKT cells participate in a variety of immune responses through cross-talk with many other innate and adaptive immune cells, including dendritic cells (DCs), natural killer (NK) cells, conventional CD4+ T cells, CD8+ T cells, B cells, neutrophils and regulatory T cells. Despite a relatively restrictive diversity in their TCR, these cells respond to vastly diverse microbial pathogens. The mechanisms underlying activation of iNKT cells at the maternal-fetal interface in inflammation-induced preterm delivery is not fully understood. In a recent study, we investigated which specific pathways were involved in decidual iNKT cell activation in a model for lipopolysaccharide (LPS)-stimulated preterm delivery. To do this, we employed an adoptive transfer system in combination with a diverse array of neutralizing antibodies (Abs) and inhibitors. We demonstrated that the activation of decidual iNKT cells requires TLR4-mediated nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK) p38 and extracellular signal-regulated kinase (ERK) pathways, the proinflammatory cytokines IL-12 and IL-18, and endogenous glycolipid antigens presented by CD1d. Our findings give new insights into the molecular mechanisms underlying iNKT cell activation during microbial infection as well as the role of iNKT cells in preterm delivery induced by inflammation. These findings underscore the promise that iNKT cell-based immunotherapies that target specific pathways utilized during iNKT cell activation could advance our ability to treat iNKT cell-associated inflammatory diseases, including preterm delivery.
{"title":"Involvement of decidual invariant NKT cells in inflammation-induced preterm delivery","authors":"Liping Li, S. Yabe, D. Schust","doi":"10.14800/ICS.843","DOIUrl":"https://doi.org/10.14800/ICS.843","url":null,"abstract":"Invariant natural killer T (iNKT) cells are a distinct lineage of αβ T lymphocytes with the capacity to recognize glycolipid antigens in the context of the atypical major histocompatibility complex (MHC) class I molecule CD1d. In response to engagement of the T cell receptor (TCR), iNKT cells efficiently and rapidly produce a broad range of cytokines and several chemokines. iNKT cells participate in a variety of immune responses through cross-talk with many other innate and adaptive immune cells, including dendritic cells (DCs), natural killer (NK) cells, conventional CD4+ T cells, CD8+ T cells, B cells, neutrophils and regulatory T cells. Despite a relatively restrictive diversity in their TCR, these cells respond to vastly diverse microbial pathogens. The mechanisms underlying activation of iNKT cells at the maternal-fetal interface in inflammation-induced preterm delivery is not fully understood. In a recent study, we investigated which specific pathways were involved in decidual iNKT cell activation in a model for lipopolysaccharide (LPS)-stimulated preterm delivery. To do this, we employed an adoptive transfer system in combination with a diverse array of neutralizing antibodies (Abs) and inhibitors. We demonstrated that the activation of decidual iNKT cells requires TLR4-mediated nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK) p38 and extracellular signal-regulated kinase (ERK) pathways, the proinflammatory cytokines IL-12 and IL-18, and endogenous glycolipid antigens presented by CD1d. Our findings give new insights into the molecular mechanisms underlying iNKT cell activation during microbial infection as well as the role of iNKT cells in preterm delivery induced by inflammation. These findings underscore the promise that iNKT cell-based immunotherapies that target specific pathways utilized during iNKT cell activation could advance our ability to treat iNKT cell-associated inflammatory diseases, including preterm delivery.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81807777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Many bacterial pathogens require adhesion to the mucosal epithelium to establish colonisation and employ numerous strategies to then avoid clearance by the host immune system. One such strategy involves expressing plasminogen receptors on the cell surface. Recently we showed that Mycoplasma hyopneumoniae is adept at capturing porcine plasminogen onto cell surface adhesins. This interaction promotes the conversion of bound plasminogen to plasmin where it plays an important role in regulating lung inflammation. Cell surface plasmin triggers a proteolytic cascade that is thought to promote dissemination of the pathogen from the initial site of colonisation. M. hyopneumoniae is a genome-reduced pathogen that has lost the genes required to synthesise amino acids and is thus reliant on the host for amino acids for growth. We have shown M. hyopneumoniae expresses a glutamyl-aminopeptidase (MHJ_0125) and a leucyl-aminopeptidase (MHJ_0461) on the extracellular surface of the cell membrane and both are perceived as playing a key role in the generation of a pool of free amino acids for growth during pathogenesis. MHJ_0461 displays a catalytic preference for leucine, phenylalanine, and methionine, whilst MHJ_0125 demonstrates a preference for glutamic acid and alanine. In addition to their catalytic functions as aminopeptidases, both enzymes bind porcine plasminogen, promoting its conversion to plasmin by tPA, and display an affinity for highly sulphated glycosaminoglycans. MHJ_0461 was also shown to bind extracellular DNA. These studies highlight the multifunctional properties of surface proteins in M. hyopneumoniae and the increasing pool of evidence that moonlighting proteins play important roles during microbial pathogenesis.
{"title":"Mycoplasmal surface-associated aminopeptidases are multifunctional moonlighting proteins","authors":"V. Jarocki, M. Padula, S. Djordjevic","doi":"10.14800/ICS.828","DOIUrl":"https://doi.org/10.14800/ICS.828","url":null,"abstract":"Many bacterial pathogens require adhesion to the mucosal epithelium to establish colonisation and employ numerous strategies to then avoid clearance by the host immune system. One such strategy involves expressing plasminogen receptors on the cell surface. Recently we showed that Mycoplasma hyopneumoniae is adept at capturing porcine plasminogen onto cell surface adhesins. This interaction promotes the conversion of bound plasminogen to plasmin where it plays an important role in regulating lung inflammation. Cell surface plasmin triggers a proteolytic cascade that is thought to promote dissemination of the pathogen from the initial site of colonisation. M. hyopneumoniae is a genome-reduced pathogen that has lost the genes required to synthesise amino acids and is thus reliant on the host for amino acids for growth. We have shown M. hyopneumoniae expresses a glutamyl-aminopeptidase (MHJ_0125) and a leucyl-aminopeptidase (MHJ_0461) on the extracellular surface of the cell membrane and both are perceived as playing a key role in the generation of a pool of free amino acids for growth during pathogenesis. MHJ_0461 displays a catalytic preference for leucine, phenylalanine, and methionine, whilst MHJ_0125 demonstrates a preference for glutamic acid and alanine. In addition to their catalytic functions as aminopeptidases, both enzymes bind porcine plasminogen, promoting its conversion to plasmin by tPA, and display an affinity for highly sulphated glycosaminoglycans. MHJ_0461 was also shown to bind extracellular DNA. These studies highlight the multifunctional properties of surface proteins in M. hyopneumoniae and the increasing pool of evidence that moonlighting proteins play important roles during microbial pathogenesis.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82626804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Crohn’s disease is a major type of inflammatory bowel disease (IBD). This disease may be associated with an inability of the intestinal mucosa to protect itself from luminal challenges or defective epithelial repair following intestinal injury. Mucosal healing relies on coordinated events consisting of intestinal epithelial cell (IEC) restitution, proliferation and differentiation. From our previous work leading to epidermal growth factor (EGF) enhancing growth performance in early-weaned pigs, we recently addressed potential in vivo mechanisms of EGF in enhancing intestine development and reducing inflammation. The mechanisms underlying the EGF-mediated protective effects were investigated by gene expression, enzyme activity, and histomorphology analyses. Further evidence linking EGFR and GLP2R to downstream signaling pathways to enhance the expression of protective luminal factors such as KGF and Muc2 was demonstrated. The multi-faceted network effect of EGFR signaling allows this receptor and its prototypical ligand, EGF, to emerge as promising targets for mucosal healing therapy.
{"title":"EGF and EGFR: Promising targets for modulating inflammation and mucosal healing therapy in IBD","authors":"Evanna Huynh, Julang Li","doi":"10.14800/ICS.840","DOIUrl":"https://doi.org/10.14800/ICS.840","url":null,"abstract":"Crohn’s disease is a major type of inflammatory bowel disease (IBD). This disease may be associated with an inability of the intestinal mucosa to protect itself from luminal challenges or defective epithelial repair following intestinal injury. Mucosal healing relies on coordinated events consisting of intestinal epithelial cell (IEC) restitution, proliferation and differentiation. From our previous work leading to epidermal growth factor (EGF) enhancing growth performance in early-weaned pigs, we recently addressed potential in vivo mechanisms of EGF in enhancing intestine development and reducing inflammation. The mechanisms underlying the EGF-mediated protective effects were investigated by gene expression, enzyme activity, and histomorphology analyses. Further evidence linking EGFR and GLP2R to downstream signaling pathways to enhance the expression of protective luminal factors such as KGF and Muc2 was demonstrated. The multi-faceted network effect of EGFR signaling allows this receptor and its prototypical ligand, EGF, to emerge as promising targets for mucosal healing therapy.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75733125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Mulder, W. Liang, P. Wielinga, L. Verschuren, K. Toet, L. Havekes, A. Hoek, R. Kleemann
Non-alcoholic steatohepatitis (NASH) is characterized by liver steatosis and lobular inflammation. It is unclear how the development of liver steatosis and the formation of inflammatory cell aggregates are related to each other. The present study investigated the longitudinal development of two forms of steatosis, micro- and macrovesicular steatosis, as well as lobular inflammation. ApoE*3Leiden.CETP (E3L.CETP) transgenic mice were fed a high-fat diet containing 1% w/w cholesterol (HFC) for 12 weeks to induce NASH. Livers were harvested in intervals of 4 weeks and analyzed by histological and biochemical techniques, as well as transcriptome and subsequent pathway analysis. Major findings were validated in independent NASH studies using other rodent models, i.e. HFD-treated C57BL/6J and LDLr ‑/- .Leiden mice. In E3L.CETP mice, microvesicular steatosis was rapidly induced and reached plateau levels after already 4 weeks of HFC treatment. By contrast, macrovesicular steatosis developed more gradually and progressed over time. Lobular inflammation increased after 4 weeks with a significant further progression towards the end of the study (12 weeks). Macrovesicular, but not microvesicular, steatosis was positively correlated with the number of inflammatory aggregates. This correlation was confirmed in a milder (C57BL/6J) and a more severe (LDLr ‑ /-.Leiden) NASH model. Furthermore, collagen staining showed onset of perihepatocellular fibrosis in E3L.CETP mice after 12 weeks of HFC treatment and transcriptome analysis substantiated the activation of pro-fibrotic pathways and genes. Macrovesicular steatosis correlated positively with liver fibrosis in LDLr-/-.Leiden mice with pronounced fibrosis. Collectively, this study shows that macrovesicular steatosis is associated with lobular inflammation and liver fibrosis in rodent models and highlights the importance of this form of steatosis in the pathogenesis of NASH.
{"title":"Macrovesicular steatosis is associated with development of lobular inflammation and fibrosis in diet-induced non-alcoholic steatohepatitis (NASH)","authors":"P. Mulder, W. Liang, P. Wielinga, L. Verschuren, K. Toet, L. Havekes, A. Hoek, R. Kleemann","doi":"10.14800/ICS.804","DOIUrl":"https://doi.org/10.14800/ICS.804","url":null,"abstract":"Non-alcoholic steatohepatitis (NASH) is characterized by liver steatosis and lobular inflammation. It is unclear how the development of liver steatosis and the formation of inflammatory cell aggregates are related to each other. The present study investigated the longitudinal development of two forms of steatosis, micro- and macrovesicular steatosis, as well as lobular inflammation. ApoE*3Leiden.CETP (E3L.CETP) transgenic mice were fed a high-fat diet containing 1% w/w cholesterol (HFC) for 12 weeks to induce NASH. Livers were harvested in intervals of 4 weeks and analyzed by histological and biochemical techniques, as well as transcriptome and subsequent pathway analysis. Major findings were validated in independent NASH studies using other rodent models, i.e. HFD-treated C57BL/6J and LDLr ‑/- .Leiden mice. In E3L.CETP mice, microvesicular steatosis was rapidly induced and reached plateau levels after already 4 weeks of HFC treatment. By contrast, macrovesicular steatosis developed more gradually and progressed over time. Lobular inflammation increased after 4 weeks with a significant further progression towards the end of the study (12 weeks). Macrovesicular, but not microvesicular, steatosis was positively correlated with the number of inflammatory aggregates. This correlation was confirmed in a milder (C57BL/6J) and a more severe (LDLr ‑ /-.Leiden) NASH model. Furthermore, collagen staining showed onset of perihepatocellular fibrosis in E3L.CETP mice after 12 weeks of HFC treatment and transcriptome analysis substantiated the activation of pro-fibrotic pathways and genes. Macrovesicular steatosis correlated positively with liver fibrosis in LDLr-/-.Leiden mice with pronounced fibrosis. Collectively, this study shows that macrovesicular steatosis is associated with lobular inflammation and liver fibrosis in rodent models and highlights the importance of this form of steatosis in the pathogenesis of NASH.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82696615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human nonfunctional pituitary adenoma (NFPA) is a common intracranial tumor and difficult in early-stage diagnosis due to barely hormone-elevation in blood, with different hormone-expressed subtypes. Hormone-related proteomic and functional variations in NFPAs were revealed with two-dimensional electrophoresis, mass spectrometry, bioinformatics, and systems biology. The proteomic and functional profiles were constructed from a follicle-stimulating hormone (FSH)-positive NFPA tissue. The variations in proteome and molecular network were analyzed among four subtypes of NFPAs (NF-, LH+, FSH+ and LH/FSH+). Those data regarding proteomic and functional variations benefit in-depth understanding of molecular mechanisms in the processes of NFPA formation and discovery of the effective biomarkers and therapeutic targets for personalized prediction, prevention, and therapy, and precision medicine practices in NFPAs.
{"title":"Hormone-related proteomic and functional variations in human nonfunctional pituitary adenomas","authors":"X. Zhan","doi":"10.14800/ICS.841","DOIUrl":"https://doi.org/10.14800/ICS.841","url":null,"abstract":"Human nonfunctional pituitary adenoma (NFPA) is a common intracranial tumor and difficult in early-stage diagnosis due to barely hormone-elevation in blood, with different hormone-expressed subtypes. Hormone-related proteomic and functional variations in NFPAs were revealed with two-dimensional electrophoresis, mass spectrometry, bioinformatics, and systems biology. The proteomic and functional profiles were constructed from a follicle-stimulating hormone (FSH)-positive NFPA tissue. The variations in proteome and molecular network were analyzed among four subtypes of NFPAs (NF-, LH+, FSH+ and LH/FSH+). Those data regarding proteomic and functional variations benefit in-depth understanding of molecular mechanisms in the processes of NFPA formation and discovery of the effective biomarkers and therapeutic targets for personalized prediction, prevention, and therapy, and precision medicine practices in NFPAs.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77265122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Goos, P. Manegold, M. Fink, F. Billmann, G. Ruf
Purpose: The purpose of this study was to assess primary healing, recurrence and continence after endoanal advancement flap repair in patients with IBD compared to those with cryptoglandular disorders. Patients and Methods: 71 patients with fistulas-in-ano received endoanal advancement flap repair between 1997 and 2009. This is a prospective, non-randomized, single-centre study. Results: Follow up data was available for 63 patients. In 46% the fistulas were due to chronic inflammatory bowel disease. 54 % had cryptoglandular fistulas. Primary healing was observed in 37 cases (58.7 %). The median time to recurrence was 27 months (mean: 45 ± 50.31) and differed significantly across the patient groups: Inflammatory bowel disease 11 months (mean: 23.65 ± 32.47), cryptoglandular origin 51 months (mean: 63.20 ± 55.84) (P < 0.01). Preoperatively, 31 (49.2 %) of the patients had impaired continence versus 30 (47.6%) postoperatively. In IBD there was no significant difference between pre- and postoperative CCIS values (pre 4.05 ± 4.12 vs 3.61 ± 4.78, P = 0.4) Conclusions: Full-thickness endoanal advancement flap repair is a successful treatment option for IBD patients with transsphincteric fistulas. Fistulas associated with chronic inflammatory bowel disease were found to have a significantly higher rate of recurrence and a shorter time to recurrence at long-term follow-up. Repeat interventions do not negatively impact postoperative continence.
目的:本研究的目的是评估IBD患者与隐腺疾病患者相比，在肛管内推进皮瓣修复后的初步愈合、复发和失禁。患者与方法:1997年至2009年，71例肛瘘患者行肛管内推进皮瓣修复术。这是一项前瞻性、非随机、单中心研究。结果:63例患者获得随访资料。46%的瘘管是由慢性炎症性肠病引起的。54%有隐腺瘘。原发性愈合37例(58.7%)。中位复发时间为27个月(平均:45±50.31)，组间差异有统计学意义:炎症性肠病11个月(平均:23.65±32.47)，隐腺源性51个月(平均:63.20±55.84)(P < 0.01)。术前31例(49.2%)患者失禁，术后30例(47.6%)患者失禁。在IBD中，术前和术后CCIS值无显著差异(4.05±4.12 vs 3.61±4.78,P = 0.4)结论:全层肛管内推进皮瓣修复是IBD经括约肌瘘患者的成功治疗选择。在长期随访中发现，慢性炎症性肠病相关瘘管的复发率明显较高，复发时间较短。重复干预对术后尿失禁没有负面影响。
{"title":"Full-thickness endoanal advancement flap repair (EAFR) in patients with IBD and fistulas-in-ano.","authors":"M. Goos, P. Manegold, M. Fink, F. Billmann, G. Ruf","doi":"10.14800/ICS.819","DOIUrl":"https://doi.org/10.14800/ICS.819","url":null,"abstract":"Purpose: The purpose of this study was to assess primary healing, recurrence and continence after endoanal advancement flap repair in patients with IBD compared to those with cryptoglandular disorders. Patients and Methods: 71 patients with fistulas-in-ano received endoanal advancement flap repair between 1997 and 2009. This is a prospective, non-randomized, single-centre study. Results: Follow up data was available for 63 patients. In 46% the fistulas were due to chronic inflammatory bowel disease. 54 % had cryptoglandular fistulas. Primary healing was observed in 37 cases (58.7 %). The median time to recurrence was 27 months (mean: 45 ± 50.31) and differed significantly across the patient groups: Inflammatory bowel disease 11 months (mean: 23.65 ± 32.47), cryptoglandular origin 51 months (mean: 63.20 ± 55.84) (P < 0.01). Preoperatively, 31 (49.2 %) of the patients had impaired continence versus 30 (47.6%) postoperatively. In IBD there was no significant difference between pre- and postoperative CCIS values (pre 4.05 ± 4.12 vs 3.61 ± 4.78, P = 0.4) Conclusions: Full-thickness endoanal advancement flap repair is a successful treatment option for IBD patients with transsphincteric fistulas. Fistulas associated with chronic inflammatory bowel disease were found to have a significantly higher rate of recurrence and a shorter time to recurrence at long-term follow-up. Repeat interventions do not negatively impact postoperative continence.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73708685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarcoidosis is a multisystem granulomatous disease of unknown origin that predominantly affects the lung, although it has the potential to involve every tissue in the body. It is characterized by the presence of non-caseating granulomas composed of a central core of epithelioid cells and multinucleated giant cells surrounded by a lymphocyte cuff at the periphery. The granulomatous reaction occurs as a defensive response against a persistent antigen in a susceptible host. Different antigenic agents for sarcoidosis have been proposed, such as infectious pathogens and/or environmental factors, without any definitive conclusion. In this research highlight we provide a brief review on the etiology and pathologic features of sarcoidosis. We also present a worthwhile rare case-report of gastrointestinal sarcoidosis, with colonic involvement causing gastrointestinal obstruction-related symptoms. We remark the importance of histologic examination to yield a diagnosis of gastrointestinal sarcoidosis, due to the non-specificity of endoscopic and radiologic findings.
{"title":"Pathologic features of sarcoidosis and a case report of unusual gastrointestinal location.","authors":"P. Erra, G. Vigliardi","doi":"10.14800/ICS.823","DOIUrl":"https://doi.org/10.14800/ICS.823","url":null,"abstract":"Sarcoidosis is a multisystem granulomatous disease of unknown origin that predominantly affects the lung, although it has the potential to involve every tissue in the body. It is characterized by the presence of non-caseating granulomas composed of a central core of epithelioid cells and multinucleated giant cells surrounded by a lymphocyte cuff at the periphery. The granulomatous reaction occurs as a defensive response against a persistent antigen in a susceptible host. Different antigenic agents for sarcoidosis have been proposed, such as infectious pathogens and/or environmental factors, without any definitive conclusion. In this research highlight we provide a brief review on the etiology and pathologic features of sarcoidosis. We also present a worthwhile rare case-report of gastrointestinal sarcoidosis, with colonic involvement causing gastrointestinal obstruction-related symptoms. We remark the importance of histologic examination to yield a diagnosis of gastrointestinal sarcoidosis, due to the non-specificity of endoscopic and radiologic findings.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77344406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Systemic and brain-localised inflammations are hallmark features of ageing that are further elevated in dementia and particularly in Alzheimer’s disease (AD). However, although present in other chronic diseases co-associated with AD, the potential role of chronic inflammation as a causative risk factor for cognitive decline and AD may have been overlooked. Peptide-derived forms of amyloid precursor protein (APP) present as amyloid beta peptides (Aβ) together with intact and peptide-derived forms of lactoferrin (Lf), are both present and co-localised in amyloid deposits in the eye and in senile plaques in the brain. It is proposed that their co-incidence supports the hypothesis that APP and Lf exert similar and mutually supportive biological roles. There is a strong evidence base for the protective role of Lf in host defence during infection with its very high affinity to ferric iron representing a front line of attack against pathogenic microbes and binding interactions that scavenge virus particles. Lf turn-over involves release of peptides exerting anti-inflammatory effects via multiple pathways, representing a ‘self-regulating’ biological system. We present compelling evidence that APP exerts a similar functional role to Lf as a signaling molecule of the innate immune system, that can account for its co-expression with Lf in AD. The hypothesis is supported by membrane-localisation of APP, metal and other ligand binding capacities, involvement in chemo-attraction of immune cells to the endothelium and cell binding to the extracellular matrix. Consistent evidence supports that systemic APP expression is correlated with inflammation status in conditions of chronic disease and ageing, and is lowered by treatments that regulate inflammation. While APP over-expression occurs in pro-inflammatory conditions other than infection, it is possible that the co-incidence of APP and Lf is specific for the presence of infection-mediated causes of APP upregulation. If APP does participate in the innate immune response, then the relationship between development of chronic inflammation and onset of APP over-expression represents a new basis for understanding AD risk. Furthermore, if substantiated, managing longitudinal changes in APP expression and amyloid-mediated AD pathology, by treating infection and chronic inflammation, offer promising targets for AD prevention and potentially therapy.
{"title":"Comparison of molecular functions of lactoferrin and amyloid precursor protein support their functional roles in the innate immune system and links with infection in Alzheimer’s disease risk.","authors":"L. Bennett, M. Bird, J. Nigro","doi":"10.14800/ICS.805","DOIUrl":"https://doi.org/10.14800/ICS.805","url":null,"abstract":"Systemic and brain-localised inflammations are hallmark features of ageing that are further elevated in dementia and particularly in Alzheimer’s disease (AD). However, although present in other chronic diseases co-associated with AD, the potential role of chronic inflammation as a causative risk factor for cognitive decline and AD may have been overlooked. Peptide-derived forms of amyloid precursor protein (APP) present as amyloid beta peptides (Aβ) together with intact and peptide-derived forms of lactoferrin (Lf), are both present and co-localised in amyloid deposits in the eye and in senile plaques in the brain. It is proposed that their co-incidence supports the hypothesis that APP and Lf exert similar and mutually supportive biological roles. There is a strong evidence base for the protective role of Lf in host defence during infection with its very high affinity to ferric iron representing a front line of attack against pathogenic microbes and binding interactions that scavenge virus particles. Lf turn-over involves release of peptides exerting anti-inflammatory effects via multiple pathways, representing a ‘self-regulating’ biological system. We present compelling evidence that APP exerts a similar functional role to Lf as a signaling molecule of the innate immune system, that can account for its co-expression with Lf in AD. The hypothesis is supported by membrane-localisation of APP, metal and other ligand binding capacities, involvement in chemo-attraction of immune cells to the endothelium and cell binding to the extracellular matrix. Consistent evidence supports that systemic APP expression is correlated with inflammation status in conditions of chronic disease and ageing, and is lowered by treatments that regulate inflammation. While APP over-expression occurs in pro-inflammatory conditions other than infection, it is possible that the co-incidence of APP and Lf is specific for the presence of infection-mediated causes of APP upregulation. If APP does participate in the innate immune response, then the relationship between development of chronic inflammation and onset of APP over-expression represents a new basis for understanding AD risk. Furthermore, if substantiated, managing longitudinal changes in APP expression and amyloid-mediated AD pathology, by treating infection and chronic inflammation, offer promising targets for AD prevention and potentially therapy.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79313315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Type II collagen (CII) is the major protein in articular cartilage. Autoantibodies to native and denatured CII (anti-CII) have been reported in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). The real meaning of the anti-CII antibodies appearance is still an open question. Anti-CII antibodies may occur more commonly very early in the disease course, suggesting that these autoantibodies could be associated with the pathophysiology of RA and JIA. This finding is supported by the fact that in collagen antibody-induced arthritis (CAIA) mouse model, immunization with anti-CII antibodies directed towards several epitopes on CII in joint cartilage can induce polyarthritis that shares several pathological features with RA. This review focuses on the inflammatory events that may be associated with anti-CII production and also the clinical application of these antibodies in RA and JIA.
{"title":"Autoantibodies to type II collagen in rheumatoid arthritis and juvenile idiopathic arthritis: Meaning and clinical interest","authors":"G. Araujo, L. Goulart, C. Ueira-Vieira","doi":"10.14800/ICS.813","DOIUrl":"https://doi.org/10.14800/ICS.813","url":null,"abstract":"Type II collagen (CII) is the major protein in articular cartilage. Autoantibodies to native and denatured CII (anti-CII) have been reported in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). The real meaning of the anti-CII antibodies appearance is still an open question. Anti-CII antibodies may occur more commonly very early in the disease course, suggesting that these autoantibodies could be associated with the pathophysiology of RA and JIA. This finding is supported by the fact that in collagen antibody-induced arthritis (CAIA) mouse model, immunization with anti-CII antibodies directed towards several epitopes on CII in joint cartilage can induce polyarthritis that shares several pathological features with RA. This review focuses on the inflammatory events that may be associated with anti-CII production and also the clinical application of these antibodies in RA and JIA.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78233726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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