title: Piperine Suppresses the Expression of CXCL8 in Lipopolysaccharide-Activated SW480 and HT-29 Cells via Downregulating the Mitogen-Activated Protein Kinase Pathways.
abstract: The anti-inflammatory effect of piperine has been largely investigated in macrophages, but its activity on epithelial cells in inflammatory settings is unclear. The present study aimed to investigate the effect of piperine on the expression of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated human epithelial-like SW480 and HT-29 cells. Our data showed that although piperine inhibited the proliferation of SW480 and HT-29 cells in a dose-dependent manner, it had low cytotoxicity on these cell lines with 50 % inhibiting concentration (IC50) values greater than 100 μM. As epithelial-like cells, SW480 and HT-29 cells secreted high levels of the chemokine CXCL8 upon LPS stimulation. Importantly, piperine dose-dependently suppressed LPS-induced secretion of CXCL8 and the expression of CXCL8 messenger RNA (mRNA). Although piperine failed to affect the critical inflammatory nuclear factor-κB pathway, it attenuated the c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signaling. Consistent with previous reports, p38 signaling seemed to play a more pronounced role on the CXCL8 expression than JNK signaling since inhibition of p38, instead of JNK, greatly suppressed LPS-induced CXCL8 expression. Collectively, our results indicated that piperine could attenuate the inflammatory response in epithelial cells via downregulating the MAPK signaling and thus the expression of CXCL8, suggesting its potential application in anti-inflammation therapy.
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Hou
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Xu
authors.forename: Qing-Bing
authors.initials: QB
authors.lastname: Zha
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: He
authors.forename: Dong-Yun
authors.initials: DY
authors.lastname: Ouyang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D052117:Benzodioxoles / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis*
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D052117:Benzodioxoles; C508606:CXCL8 protein, human; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C008922:piperine