title: The increased mucosal mRNA expressions of complement C3 and interleukin-17 in inflammatory bowel disease.
abstract: Recent studies have demonstrated that the complement system participates in the regulation of T cell functions. To address the local biosynthesis of complement components in inflammatory bowel disease (IBD) mucosa, we investigated C3 and interleukin (IL)-17 mRNA expression in mucosal samples obtained from patients with IBD. The molecular mechanisms underlying C3 induction were investigated in human colonic subepithelial myofibroblasts (SEMFs). IL-17 and C3 mRNA expressions in the IBD mucosa were evaluated by real-time polymerase chain reaction. The C3 levels in the supernatant were determined by enzyme-linked immunosorbent assay. IL-17 and C3 mRNA expressions were elevated significantly in the active lesions from ulcerative colitis (UC) and Crohn's disease (CD) patients. There was a significant positive correlation between IL-17 and C3 mRNA expression in the IBD mucosa. IL-17 stimulated a dose- and time-dependent increase in C3 mRNA expression and C3 secretion in colonic SEMFs. The C3 molecules secreted by colonic SEMFs were a 115-kDa alpha-chain linked to a 70-kDa beta-chain by disulphide bonds, which was identical to serum C3. The IL-17-induced C3 mRNA expression was blocked by p42/44 mitogen-activated protein kinase (MAPK) inhibitors (PD98059 and U0216) and a p38 MAPK inhibitor (SB203580). Furthermore, IL-17-induced C3 mRNA expression was inhibited by an adenovirus containing a stable mutant form of I kappaB alpha. C3 and IL-17 mRNA expressions are enhanced, with a strong correlation, in the inflamed mucosa of IBD patients. Part of these clinical findings was considered to be mediated by the colonic SEMF response to IL-17.
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sugihara
authors.forename: A
authors.initials: A
authors.lastname: Kobori
authors.forename: H
authors.initials: H
authors.lastname: Imaeda
authors.forename: T
authors.initials: T
authors.lastname: Tsujikawa
authors.forename: K
authors.initials: K
authors.lastname: Amagase
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiyama
authors.forename: A
authors.initials: A
authors.lastname: Andoh
mesh_terms: D000256:Adenoviridae; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003176:Complement C3 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009154:Mutation; D000072000:NF-KappaB Inhibitor alpha; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014161:Transduction, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D003176:Complement C3; D004791:Enzyme Inhibitors; D005419:Flavonoids; D020672:I-kappa B Proteins; D007093:Imidazoles; D020381:Interleukin-17; C000606204:NFKBIA protein, human; D011725:Pyridines; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one