Caroline L de Lima, Bruna R Amorim, Carine Royer, Augusto P Resende, Maria F Borin, Francisco A R Neves, Ana Carolina Acevedo
{"title":"人牙髓细胞中PPARβ/δ的初步体外研究","authors":"Caroline L de Lima, Bruna R Amorim, Carine Royer, Augusto P Resende, Maria F Borin, Francisco A R Neves, Ana Carolina Acevedo","doi":"10.1155/2021/8854921","DOIUrl":null,"url":null,"abstract":"<p><p>Controlling the inflammatory response to restore tissue homeostasis is a crucial step to maintain tooth vitality after pathogen removal from caries-affected dental tissues. The nuclear peroxisome proliferator-activated receptor beta/delta (PPAR<i>β</i>/<i>δ</i>) is a ligand-activated transcription factor with emerging anti-inflammatory roles in many cells and tissues. However, its expression and functions are poorly understood in human dental pulp cells (hDPCs). Thus, this study evaluated PPAR<i>β</i>/<i>δ</i> expression and assessed the anti-inflammatory effects evoked by activation of PPAR<i>β</i>/<i>δ</i> in lipopolysaccharide- (LPS-) induced hDPCs. Our results showed that hDPCs constitutively expressed PPAR<i>β</i>/<i>δ</i> mRNA/protein, and treatment with LPS increased <i>PPARβ/δ</i> mRNA expression. The selective PPAR<i>β</i>/<i>δ</i> agonist GW0742 significantly decreased inflammation-related mRNA expression in hDPCs (<i>IL6</i>, <i>IL1β</i>, <i>TNFα</i>, <i>MMP1</i>, and <i>MMP2</i>) and RAW264.7 cells (<i>Il6</i> and <i>Tnfα</i>). Further, PPAR<i>β</i>/<i>δ</i> agonist attenuated MMP2/9 gelatinolytic activity in hDPCs. Previously LPS-conditioned hDPCs increased the migration of RAW264.7 cells through the membrane of a Transwell coculture system. Conversely, pretreatment with GW0742 markedly decreased macrophage recruitment. These findings provide among the first evidence that hDPCs express PPAR<i>β</i>/<i>δ</i>. In addition, they suggest that activation of PPAR<i>β</i>/<i>δ</i> by GW0742 can attenuate some cellular and molecular in vitro aspects related to the inflammatory process, pointing out to investigate its potential target role in dental pulp inflammation.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2021-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997762/pdf/","citationCount":"0","resultStr":"{\"title\":\"Investigation of PPAR<i>β</i>/<i>δ</i> within Human Dental Pulp Cells: A Preliminary In Vitro Study.\",\"authors\":\"Caroline L de Lima, Bruna R Amorim, Carine Royer, Augusto P Resende, Maria F Borin, Francisco A R Neves, Ana Carolina Acevedo\",\"doi\":\"10.1155/2021/8854921\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Controlling the inflammatory response to restore tissue homeostasis is a crucial step to maintain tooth vitality after pathogen removal from caries-affected dental tissues. The nuclear peroxisome proliferator-activated receptor beta/delta (PPAR<i>β</i>/<i>δ</i>) is a ligand-activated transcription factor with emerging anti-inflammatory roles in many cells and tissues. However, its expression and functions are poorly understood in human dental pulp cells (hDPCs). Thus, this study evaluated PPAR<i>β</i>/<i>δ</i> expression and assessed the anti-inflammatory effects evoked by activation of PPAR<i>β</i>/<i>δ</i> in lipopolysaccharide- (LPS-) induced hDPCs. Our results showed that hDPCs constitutively expressed PPAR<i>β</i>/<i>δ</i> mRNA/protein, and treatment with LPS increased <i>PPARβ/δ</i> mRNA expression. The selective PPAR<i>β</i>/<i>δ</i> agonist GW0742 significantly decreased inflammation-related mRNA expression in hDPCs (<i>IL6</i>, <i>IL1β</i>, <i>TNFα</i>, <i>MMP1</i>, and <i>MMP2</i>) and RAW264.7 cells (<i>Il6</i> and <i>Tnfα</i>). Further, PPAR<i>β</i>/<i>δ</i> agonist attenuated MMP2/9 gelatinolytic activity in hDPCs. Previously LPS-conditioned hDPCs increased the migration of RAW264.7 cells through the membrane of a Transwell coculture system. Conversely, pretreatment with GW0742 markedly decreased macrophage recruitment. These findings provide among the first evidence that hDPCs express PPAR<i>β</i>/<i>δ</i>. In addition, they suggest that activation of PPAR<i>β</i>/<i>δ</i> by GW0742 can attenuate some cellular and molecular in vitro aspects related to the inflammatory process, pointing out to investigate its potential target role in dental pulp inflammation.</p>\",\"PeriodicalId\":20439,\"journal\":{\"name\":\"PPAR Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2021-03-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997762/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"PPAR Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1155/2021/8854921\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2021/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"PPAR Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2021/8854921","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Investigation of PPARβ/δ within Human Dental Pulp Cells: A Preliminary In Vitro Study.
Controlling the inflammatory response to restore tissue homeostasis is a crucial step to maintain tooth vitality after pathogen removal from caries-affected dental tissues. The nuclear peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is a ligand-activated transcription factor with emerging anti-inflammatory roles in many cells and tissues. However, its expression and functions are poorly understood in human dental pulp cells (hDPCs). Thus, this study evaluated PPARβ/δ expression and assessed the anti-inflammatory effects evoked by activation of PPARβ/δ in lipopolysaccharide- (LPS-) induced hDPCs. Our results showed that hDPCs constitutively expressed PPARβ/δ mRNA/protein, and treatment with LPS increased PPARβ/δ mRNA expression. The selective PPARβ/δ agonist GW0742 significantly decreased inflammation-related mRNA expression in hDPCs (IL6, IL1β, TNFα, MMP1, and MMP2) and RAW264.7 cells (Il6 and Tnfα). Further, PPARβ/δ agonist attenuated MMP2/9 gelatinolytic activity in hDPCs. Previously LPS-conditioned hDPCs increased the migration of RAW264.7 cells through the membrane of a Transwell coculture system. Conversely, pretreatment with GW0742 markedly decreased macrophage recruitment. These findings provide among the first evidence that hDPCs express PPARβ/δ. In addition, they suggest that activation of PPARβ/δ by GW0742 can attenuate some cellular and molecular in vitro aspects related to the inflammatory process, pointing out to investigate its potential target role in dental pulp inflammation.
期刊介绍:
PPAR Research is a peer-reviewed, Open Access journal that publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated receptors (PPARs), as well as their role in the regulation of cellular differentiation, development, energy homeostasis and metabolic function. The journal also welcomes preclinical and clinical trials of drugs that can modulate PPAR activity, with a view to treating chronic diseases and disorders such as dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity.