Efrossini Nomikou, A. Alexopoulou, L. Vasilieva, S. Dourakis
CD146, an element of the endothelial junction- has been evaluated in several pathological conditions with altered endothelial function but never before in patients with liver disease. As angiogenesis and inflammation were implicated in the development of liver fibrosis, we have explored this suggestion by evaluating levels of sCD146 in a group of patients with chronic liver diseases (CLD) and in cirrhotic patients. The results indicated that there is a clear connection between sCD146 levels and the progression of liver disease. They can differentiate noncirrhotic patients with CLD from cirrhotics, supporting the usefulness of CD146 in the noninvasive diagnosis of liver cirrhosis. Furthermore, our findings provided evidence of sCD146 upregulation in decompensated compared to compensated cirrhosis and sCD146 values were clearly associated with Model for End Stage Liver Disease (MELD) score. Thus, by using an easy to perform ELISA method, we demonstrated that sCD146 can accurately distinguish advanced fibrosis and prognosticate decompensation in cirrhosis.
{"title":"Endothelial biomarker soluble CD146 suggests that angiogenesis plays an important role in progression of fibrosis in liver disease","authors":"Efrossini Nomikou, A. Alexopoulou, L. Vasilieva, S. Dourakis","doi":"10.14800/ICS.925","DOIUrl":"https://doi.org/10.14800/ICS.925","url":null,"abstract":"CD146, an element of the endothelial junction- has been evaluated in several pathological conditions with altered endothelial function but never before in patients with liver disease. As angiogenesis and inflammation were implicated in the development of liver fibrosis, we have explored this suggestion by evaluating levels of sCD146 in a group of patients with chronic liver diseases (CLD) and in cirrhotic patients. The results indicated that there is a clear connection between sCD146 levels and the progression of liver disease. They can differentiate noncirrhotic patients with CLD from cirrhotics, supporting the usefulness of CD146 in the noninvasive diagnosis of liver cirrhosis. Furthermore, our findings provided evidence of sCD146 upregulation in decompensated compared to compensated cirrhosis and sCD146 values were clearly associated with Model for End Stage Liver Disease (MELD) score. Thus, by using an easy to perform ELISA method, we demonstrated that sCD146 can accurately distinguish advanced fibrosis and prognosticate decompensation in cirrhosis.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75045196","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}
Inflammation contributes a significant part to the advancement of diabetic kidney disease (DKD), yet relatively little is known about the root cause of these inflammatory events. Serum Amyloid A (SAA) triggers a potent inflammatory response in a variety of tissues and is up-regulated in glomerular and tubulointerstitial compartments of the diabetic kidney. Under inflammatory conditions, podocytes, along with other intrinsic cells, produce SAA locally in the kidney. Our recent work has shown that SAA induces NF-κB activation and subsequent inflammatory chemokines and cytokines in cultured podocytes. Recent evidence suggests that local production of SAA in diabetes may lead to monocyte and macrophage recruitment, neutrophil activation, and other related incidents resulting in sustained chronic inflammatory conditions in the kidney which may further exacerbate DKD.
{"title":"An Inflammatory Nexus: Serum Amyloid A and inflammation in Diabetic Kidney Disease","authors":"R. Anderberg, B. Dieter, R. Meek, K. Tuttle","doi":"10.14800/ICS.959","DOIUrl":"https://doi.org/10.14800/ICS.959","url":null,"abstract":"Inflammation contributes a significant part to the advancement of diabetic kidney disease (DKD), yet relatively little is known about the root cause of these inflammatory events. Serum Amyloid A (SAA) triggers a potent inflammatory response in a variety of tissues and is up-regulated in glomerular and tubulointerstitial compartments of the diabetic kidney. Under inflammatory conditions, podocytes, along with other intrinsic cells, produce SAA locally in the kidney. Our recent work has shown that SAA induces NF-κB activation and subsequent inflammatory chemokines and cytokines in cultured podocytes. Recent evidence suggests that local production of SAA in diabetes may lead to monocyte and macrophage recruitment, neutrophil activation, and other related incidents resulting in sustained chronic inflammatory conditions in the kidney which may further exacerbate DKD.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85336126","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}
Stem cell transplantation has been applied to clinical trials and obtained certain curative effect, but due to the severe environmental such as oxidative stress, the efficiency of stem cell transplantation is still low. However, oxidative stress on stem cells, the influence of the transplantation efficiency and its molecular mechanism are not fully understood. In our recent research, we have confirmed that oxidative stress is the mainly reason that caused the low efficiency of hUCMSCs transplantation. In vitro, antioxidants pretreatment of the hUCMSCs can decrease cell apoptosis through the MAPK-PKC-Nrf2 pathway. In vivo, antioxidants pretreatment can accelerate the host hepatic regenerative process and improve the expansion efficiency of stem cells. In this research, the antioxidant we used is edaravone which is now widely used in clinic. Thus, our study has answered how the oxidative stress affects stem cell transplantation efficiency and puts forward a clinical antioxidant which can improve the endogenous antioxidant level of stem cells.
{"title":"Endogenous antioxidant level of stem cell is important for the transplantation efficacy","authors":"Min Yang, Jia Xiao, Yingxia Liu","doi":"10.14800/ICS.946","DOIUrl":"https://doi.org/10.14800/ICS.946","url":null,"abstract":"Stem cell transplantation has been applied to clinical trials and obtained certain curative effect, but due to the severe environmental such as oxidative stress, the efficiency of stem cell transplantation is still low. However, oxidative stress on stem cells, the influence of the transplantation efficiency and its molecular mechanism are not fully understood. In our recent research, we have confirmed that oxidative stress is the mainly reason that caused the low efficiency of hUCMSCs transplantation. In vitro, antioxidants pretreatment of the hUCMSCs can decrease cell apoptosis through the MAPK-PKC-Nrf2 pathway. In vivo, antioxidants pretreatment can accelerate the host hepatic regenerative process and improve the expansion efficiency of stem cells. In this research, the antioxidant we used is edaravone which is now widely used in clinic. Thus, our study has answered how the oxidative stress affects stem cell transplantation efficiency and puts forward a clinical antioxidant which can improve the endogenous antioxidant level of stem cells.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91415432","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}
R. Aktimur, Süleyman Çetinkünar, K. Yildirim, S. Özdaş, S. Aktimur, Ali Kağan Gökakın
In order to reduce negative appendectomy (NA) rate, red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) were investigated. But, their combined role on the differential diagnosis of acute appendicitis (AA) with a control group of NA have not been established. A total of 530 patients who underwent appendectomy with the pre-diagnosis of AA were retrospectively analyzed and divided into two groups: 1) 469 AA, and 2) 61 NA. Diagnostic value of statistically significant parameters, white blood cell (WBC) and MPV were analyzed with ROC analysis. Median WBC and mean MPV values were found to be significantly higher in AA group (12.9 /μL, range: 3.4-83.7 vs. 11 /μL, range: 3.4-39.9; and 9.6±1.5 fL vs. 9.1±1.5 fL) ( P =0.002 and 0.018). Mean RDW and median NLR were found to be similar. Combined sensitivity, specificity, positive predictive value and negative predictive value of WBC and MPV for recommended cut-off values were 67.4%, 72.7%, 96.1% and 17.9%, respectively. Among other inflammation related CBC parameters, increased MPV and its combination with WBC may be used as a valuable tool for the differential diagnosis of AA.
为降低阑尾切除阴性(NA)率，观察红细胞分布宽度(RDW)、中性粒细胞与淋巴细胞比值(NLR)和平均血小板体积(MPV)。但是，它们在与NA对照组的急性阑尾炎(AA)鉴别诊断中的联合作用尚未得到证实。回顾性分析530例术前诊断为AA的阑尾切除术患者，分为AA组469例和NA组61例。采用ROC分析对具有统计学意义的参数、白细胞(WBC)和MPV的诊断价值进行分析。AA组中位WBC和平均MPV值显著高于AA组(12.9 /μL，范围3.4 ~ 83.7 vs. 11 /μL，范围3.4 ~ 39.9;9.6±1.5 fL vs 9.1±1.5 fL) (P =0.002和0.018)。平均RDW和中位NLR相似。WBC和MPV对推荐临界值的敏感性、特异性、阳性预测值和阴性预测值分别为67.4%、72.7%、96.1%和17.9%。在其他与炎症相关的CBC参数中，MPV升高及其与WBC的结合可作为鉴别诊断AA的有价值的工具。
{"title":"Mean platelet volume is a significant biomarker in the differential diagnosis of acute appendicitis","authors":"R. Aktimur, Süleyman Çetinkünar, K. Yildirim, S. Özdaş, S. Aktimur, Ali Kağan Gökakın","doi":"10.14800/ICS.930","DOIUrl":"https://doi.org/10.14800/ICS.930","url":null,"abstract":"In order to reduce negative appendectomy (NA) rate, red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) were investigated. But, their combined role on the differential diagnosis of acute appendicitis (AA) with a control group of NA have not been established. A total of 530 patients who underwent appendectomy with the pre-diagnosis of AA were retrospectively analyzed and divided into two groups: 1) 469 AA, and 2) 61 NA. Diagnostic value of statistically significant parameters, white blood cell (WBC) and MPV were analyzed with ROC analysis. Median WBC and mean MPV values were found to be significantly higher in AA group (12.9 /μL, range: 3.4-83.7 vs. 11 /μL, range: 3.4-39.9; and 9.6±1.5 fL vs. 9.1±1.5 fL) ( P =0.002 and 0.018). Mean RDW and median NLR were found to be similar. Combined sensitivity, specificity, positive predictive value and negative predictive value of WBC and MPV for recommended cut-off values were 67.4%, 72.7%, 96.1% and 17.9%, respectively. Among other inflammation related CBC parameters, increased MPV and its combination with WBC may be used as a valuable tool for the differential diagnosis of AA.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78633951","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}
N. T. Pietrani, K. F. Rodrigues, A. Bosco, C. M. A. F. Vieira, L. Perucci, M. Oliveira, A. Teixeira, A. Ferreira, K. Gomes, L. Sousa
Background : We investigated the activation of intracellular signaling pathways in individuals with and without T2D/obesity and correlated them with clinical characteristics and IL6, IL10 and TNFα serum levels. Methods : This study included 42 patients with T2D and 42 healthy controls matched by BMI. I ntracellular signaling pathways Akt, p38 and ERK in peripheral blood mononuclear cells (PBMCs); IL6, IL10 and TNFα serum levels were evaluated. R esults: Western blot analysis revealed that phosphorylation values of Akt, p38 and ERK were not significant different between the groups; but, once individuals were stratified according to BMI, activation of Akt and ERK was associated with obesity and T2D while the activation of p38 with obesity. The phosphorylation values of these proteins were also positively correlated with BMI and waist circumference. IL6 levels correlated with P-p38 in control group, while IL10 and TNF-a did not correlated with these pathways. Conclusions : These results suggest that there is a link among obesity, T2D and intracellular signaling pathways in peripheral circulating immune cells, which may be associated with systemic low grade inflammation observed in T2D and obese patients.
{"title":"Peripheral activation of inflammatory intracellular signaling pathways and their correlation with IL6, IL10 and TNFα in obesity and type 2 diabetes mellitus","authors":"N. T. Pietrani, K. F. Rodrigues, A. Bosco, C. M. A. F. Vieira, L. Perucci, M. Oliveira, A. Teixeira, A. Ferreira, K. Gomes, L. Sousa","doi":"10.14800/ICS.926","DOIUrl":"https://doi.org/10.14800/ICS.926","url":null,"abstract":"Background : We investigated the activation of intracellular signaling pathways in individuals with and without T2D/obesity and correlated them with clinical characteristics and IL6, IL10 and TNFα serum levels. Methods : This study included 42 patients with T2D and 42 healthy controls matched by BMI. I ntracellular signaling pathways Akt, p38 and ERK in peripheral blood mononuclear cells (PBMCs); IL6, IL10 and TNFα serum levels were evaluated. R esults: Western blot analysis revealed that phosphorylation values of Akt, p38 and ERK were not significant different between the groups; but, once individuals were stratified according to BMI, activation of Akt and ERK was associated with obesity and T2D while the activation of p38 with obesity. The phosphorylation values of these proteins were also positively correlated with BMI and waist circumference. IL6 levels correlated with P-p38 in control group, while IL10 and TNF-a did not correlated with these pathways. Conclusions : These results suggest that there is a link among obesity, T2D and intracellular signaling pathways in peripheral circulating immune cells, which may be associated with systemic low grade inflammation observed in T2D and obese patients.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82743371","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}
Inflammatory response is responsible for many pathological events and diseases, characterized by overexpression of pro-inflammatory cytokines. Rac1, a molecule mediating many intracellular signaling pathways, has a tight relationship with inflammation. Over the past decade, many researchers have demonstrated that Rac1 plays a critical role in the initiation and progression of inflammation and sepsis including the cytoskeletal rearrangement, Nox activation and ROS production, activation of NF-κB and release of pro-inflammatory cytokines, phagocytosis, and efferocytosis. In addition, Rac1 is also involved in other mechanisms of inflammation, like angiogenesis, apoptosis, and the invasiveness of the pathogen. Interestingly, Rac1 plays both positive and negative roles in regulating inflammation. Finally, Rac1 as a potent pharmacological target was reviewed. Some clinical and experimental studies showed that inhibition of Rac1 had a protective effect on inflammatory diseases. In summary, all data suggest that Rac1 is a crucial factor in different kinds and stages of inflammatory responses.
{"title":"The conflicting role of Rac1 in inflammation","authors":"Chaoyi Qin, Ruiqi Liu, Hanmin Liu","doi":"10.14800/ICS.922","DOIUrl":"https://doi.org/10.14800/ICS.922","url":null,"abstract":"Inflammatory response is responsible for many pathological events and diseases, characterized by overexpression of pro-inflammatory cytokines. Rac1, a molecule mediating many intracellular signaling pathways, has a tight relationship with inflammation. Over the past decade, many researchers have demonstrated that Rac1 plays a critical role in the initiation and progression of inflammation and sepsis including the cytoskeletal rearrangement, Nox activation and ROS production, activation of NF-κB and release of pro-inflammatory cytokines, phagocytosis, and efferocytosis. In addition, Rac1 is also involved in other mechanisms of inflammation, like angiogenesis, apoptosis, and the invasiveness of the pathogen. Interestingly, Rac1 plays both positive and negative roles in regulating inflammation. Finally, Rac1 as a potent pharmacological target was reviewed. Some clinical and experimental studies showed that inhibition of Rac1 had a protective effect on inflammatory diseases. In summary, all data suggest that Rac1 is a crucial factor in different kinds and stages of inflammatory responses.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82509473","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}
The majority of deaths developing in autoimmune diseases are caused by cardiovascular reasons, with a close relationship to this disease group. Chronic inflammation in autoimmune diseases and the inflammatory process observed in atherosclerosis have similar characteristics, and the early premature formation of atherosclerosis is one of the most important results affecting mortality in this patient group. The observation of early atherosclerosis even before clinical signs of disease means that early diagnosis and treatment choices will be the cause of stopping or slowing the progression of disease. Thus manifestations of endothelial dysfunction, development of atherosclerosis, and development of acute coronary syndrome which affect mortality and morbidity will be reduced to a minimum. In this review we aim to evaluate some tests used for early diagnosis and treatment choices in terms of the effect on disease progression in this patient group. Keywords: Premature atherosclerosis, autoimmune disease, cardiovascular disease
{"title":"Cardiovascular Risk in Patients Affected by Autoimmune Diseases Early Diagnosis and Treatment","authors":"T. Kurt, F. Gökmen","doi":"10.14800/ICS.920","DOIUrl":"https://doi.org/10.14800/ICS.920","url":null,"abstract":"The majority of deaths developing in autoimmune diseases are caused by cardiovascular reasons, with a close relationship to this disease group. Chronic inflammation in autoimmune diseases and the inflammatory process observed in atherosclerosis have similar characteristics, and the early premature formation of atherosclerosis is one of the most important results affecting mortality in this patient group. The observation of early atherosclerosis even before clinical signs of disease means that early diagnosis and treatment choices will be the cause of stopping or slowing the progression of disease. Thus manifestations of endothelial dysfunction, development of atherosclerosis, and development of acute coronary syndrome which affect mortality and morbidity will be reduced to a minimum. In this review we aim to evaluate some tests used for early diagnosis and treatment choices in terms of the effect on disease progression in this patient group. Keywords: Premature atherosclerosis, autoimmune disease, cardiovascular disease","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75612462","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}
G. Fabbrocini, M. Galliano, M. Aries, C. Vaissière, N. Castex‐Rizzi, H. Duplan, C. Coutanceau, S. Bessou-Touya, F. Schmitt, M. Saint-Aroman
Purpose of the study: The objective of this study was to review the recent evidence regarding the pathophysiology of reactive skin, acne vulgaris and rosacea, with a focus on the link between the impaired skin barrier and the inflammasome. In this context, we evaluated the activity of Rhealba ® oat plantlet extract on the inflammasome in vitro . Procedures: Using an in vitro inflammatory model of Reconstructed Human Epidermis (RHE), we explored the biologically active mature forms of inflammasome products, IL-1b and IL-18 cytokines, in parallel with inflammatory mediators IL-6, IL-8, TNF-a, VEGF-A, MIP-1a/CCL3, sICAM-1. Results: We showed that a 2-h pre-treatment with Rhealba ® oat plantlet extract with Vitamin E and A-DERMA cream for reactive skin significantly blocked poly I:C-induced up-regulation of inflammasome cytokines and inflammatory mediators, as we observed IL18, IL6, IL8, TNFa, VEGF-A, MIP-1a, sICAM-1 down-regulation, along with a significant reduction of IL1-b. Conclusions and message of the paper: We propose that reactive skin, rosacea and acne share skin barrier and innate immunity dysfunctions. Moreover, the results suggest that Rhealba ® Oat plantlet extract provides an adapted solution for the treatment of reactive skin, and probably for the other skin disorders involving inflammasome pathway activation.
{"title":"Fragility of the epidermis, a common pathophysiological mechanism of acne vulgaris, rosacea and reactive skin involving inflammasome activation","authors":"G. Fabbrocini, M. Galliano, M. Aries, C. Vaissière, N. Castex‐Rizzi, H. Duplan, C. Coutanceau, S. Bessou-Touya, F. Schmitt, M. Saint-Aroman","doi":"10.14800/ICS.909","DOIUrl":"https://doi.org/10.14800/ICS.909","url":null,"abstract":"Purpose of the study: The objective of this study was to review the recent evidence regarding the pathophysiology of reactive skin, acne vulgaris and rosacea, with a focus on the link between the impaired skin barrier and the inflammasome. In this context, we evaluated the activity of Rhealba ® oat plantlet extract on the inflammasome in vitro . Procedures: Using an in vitro inflammatory model of Reconstructed Human Epidermis (RHE), we explored the biologically active mature forms of inflammasome products, IL-1b and IL-18 cytokines, in parallel with inflammatory mediators IL-6, IL-8, TNF-a, VEGF-A, MIP-1a/CCL3, sICAM-1. Results: We showed that a 2-h pre-treatment with Rhealba ® oat plantlet extract with Vitamin E and A-DERMA cream for reactive skin significantly blocked poly I:C-induced up-regulation of inflammasome cytokines and inflammatory mediators, as we observed IL18, IL6, IL8, TNFa, VEGF-A, MIP-1a, sICAM-1 down-regulation, along with a significant reduction of IL1-b. Conclusions and message of the paper: We propose that reactive skin, rosacea and acne share skin barrier and innate immunity dysfunctions. Moreover, the results suggest that Rhealba ® Oat plantlet extract provides an adapted solution for the treatment of reactive skin, and probably for the other skin disorders involving inflammasome pathway activation.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90487654","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}
F. Guzmán-Mejía, C. López-Rubalcava, C. González-Espinosa
Mast cells (MC) play an important role on allergic reactions triggered by the IgE/Antigen-dependent crosslinking of the high affinity IgE receptor (FceRI), and their participation on inflammatory innate immune responses triggered by Toll-like receptors (TLRs) has started to be documented. Physiological conditions such as stress exert a modulatory effect on allergic reactions since stress mediators activate signaling cascades that either interfere or potentiate the FceRI-dependent cytokine production. Recently, the effect of stress mediators on cytokine production induced after Toll-like receptors (TLRs) has started to be addressed in this cell type. In a recent paper, we analyzed the effects of stress induced by forced swimming (FS) on the MC-dependent production of Tumor Necrosis Factor (TNF) induced by a single intraperitoneal injection of bacterial lipopolysaccharide (LPS) in mice. FS provoked an immediate and transient inhibition of LPS-elicited TNF accumulation in peritoneum, which lasted around to 30 min. With the aim to identify the mediator of stress responsible for the inhibition, we first blocked catecholamine release from adrenal glands (by adrenalectomy) or nerve terminals (with DSP4 treatment). With these manipulations we observed an important increase on basal ip TNF levels and enhanced LPS-induced TNF release without any effect on stress-induced inhibitory effects. We then pre-treated animals with the glucocorticoid receptor antagonist mifepristone and did not observe any change on basal levels or stress-induced inhibition of TNF release. Finally, we administered an antagonist of acetylcholine receptors (mecamylamine) and observed an increase on basal levels of ip TNF values together with an important blockage of stress effects. Those results show for the first time that early MC-derived TNF secretion after Toll-like receptors is negatively controlled by adrenaline and transiently inhibited by the anti-inflammatory cholinergic reflex. Our results adds to the description of stress effects on MC activation and open new avenues in the research on the control of chronic inflammatory reactions associated with long term MC-dependent cytokine secretion.
{"title":"Stress-dependent control of cytokine production in mast cells stimulated through FceRI and Toll-like 4 receptors","authors":"F. Guzmán-Mejía, C. López-Rubalcava, C. González-Espinosa","doi":"10.14800/ICS.881","DOIUrl":"https://doi.org/10.14800/ICS.881","url":null,"abstract":"Mast cells (MC) play an important role on allergic reactions triggered by the IgE/Antigen-dependent crosslinking of the high affinity IgE receptor (FceRI), and their participation on inflammatory innate immune responses triggered by Toll-like receptors (TLRs) has started to be documented. Physiological conditions such as stress exert a modulatory effect on allergic reactions since stress mediators activate signaling cascades that either interfere or potentiate the FceRI-dependent cytokine production. Recently, the effect of stress mediators on cytokine production induced after Toll-like receptors (TLRs) has started to be addressed in this cell type. In a recent paper, we analyzed the effects of stress induced by forced swimming (FS) on the MC-dependent production of Tumor Necrosis Factor (TNF) induced by a single intraperitoneal injection of bacterial lipopolysaccharide (LPS) in mice. FS provoked an immediate and transient inhibition of LPS-elicited TNF accumulation in peritoneum, which lasted around to 30 min. With the aim to identify the mediator of stress responsible for the inhibition, we first blocked catecholamine release from adrenal glands (by adrenalectomy) or nerve terminals (with DSP4 treatment). With these manipulations we observed an important increase on basal ip TNF levels and enhanced LPS-induced TNF release without any effect on stress-induced inhibitory effects. We then pre-treated animals with the glucocorticoid receptor antagonist mifepristone and did not observe any change on basal levels or stress-induced inhibition of TNF release. Finally, we administered an antagonist of acetylcholine receptors (mecamylamine) and observed an increase on basal levels of ip TNF values together with an important blockage of stress effects. Those results show for the first time that early MC-derived TNF secretion after Toll-like receptors is negatively controlled by adrenaline and transiently inhibited by the anti-inflammatory cholinergic reflex. Our results adds to the description of stress effects on MC activation and open new avenues in the research on the control of chronic inflammatory reactions associated with long term MC-dependent cytokine secretion.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91382508","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}
Glucocorticoid (GC) hormone exerts numerous physiological roles that include modulation of immune, nervous, cardiovascular and metabolic systems. Synthetic GCs such as dexamethasone and prednisone/prednisolone are widely prescribed in the clinical context to the treatment of inflammatory-related diseases. In spite of its positive therapeutic effect, GC-based therapies may cause several adverse effects including glucose intolerance and peripheral insulin resistance. Reduction of insulin sensitivity in the adipocytes and adipose tissue caused by GC treatment is associated with increased lipolysis and abnormal Ser phosphorylation of insulin substrate receptor (IRS)-1 and protein kinase B (PKB). However, there is no consensus about the precise mechanisms whereby GC treatment promotes such attenuation in the insulin signaling pathway. In this paper, we will briefly discuss and present some molecular evidences that might be involved with this negative impact of GC in the insulin signaling in the adipose tissue.
{"title":"How much we know about the attenuation of insulin signaling in the adipose tissue caused by glucocorticoid treatment","authors":"A. Rafacho, E. Nunes, S. Bordin","doi":"10.14800/ICS.879","DOIUrl":"https://doi.org/10.14800/ICS.879","url":null,"abstract":"Glucocorticoid (GC) hormone exerts numerous physiological roles that include modulation of immune, nervous, cardiovascular and metabolic systems. Synthetic GCs such as dexamethasone and prednisone/prednisolone are widely prescribed in the clinical context to the treatment of inflammatory-related diseases. In spite of its positive therapeutic effect, GC-based therapies may cause several adverse effects including glucose intolerance and peripheral insulin resistance. Reduction of insulin sensitivity in the adipocytes and adipose tissue caused by GC treatment is associated with increased lipolysis and abnormal Ser phosphorylation of insulin substrate receptor (IRS)-1 and protein kinase B (PKB). However, there is no consensus about the precise mechanisms whereby GC treatment promotes such attenuation in the insulin signaling pathway. In this paper, we will briefly discuss and present some molecular evidences that might be involved with this negative impact of GC in the insulin signaling in the adipose tissue.","PeriodicalId":13679,"journal":{"name":"Inflammation and cell signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88003051","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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