Intestinal gene expression of IL17A, IL17F, IL23A and TLR9 in inflammatory bowel diseases

[S. Dragašević]

128 listova

Medicina - Molekularna medicina /

Zapaljenske bolesti creva (ZBC) su hronične, idiopatske bolesti u koje spadaju Kronova bolest (KB) i ulcerozni kolitis (UK). Nastanak ZBC je posledica poremećenog imunološkog odgovora na intestinalnu mikrofloru kod genetički predisponiranog domaćina. Signalna interakcija Toll-like receptora 9 (TLR9), interleukina (IL)-23 i IL-17 u patogenezi ZBC nije u potpunosti razjašnjena. Cilj ove studije bio je ispitivanje razlika u ekspresiji gena IL17A, IL17F, IL23A i TLR9 između inflamirane i neinflamirane mukoze intestinuma kod pacijenata sa endoskopski aktivnom ZBC. Dodatni cilj bila je asocijacija nivoa ekspresije ovih gena sa kliničkim parametrima ZBC. S obzirom da je odnos IL17A i IL17F važan za regulaciju zapaljenskog procesa, još jedan od ciljeva bila je procena međusobnog odnosa ekspresije navedenih gena u inflamiranoj i neinflamiranoj mukozi ZBC. U studiju je bilo uključeno 104 novodijagnostikovana pacijenata sa ZBC (50 KB, 54 UK). Ispitivanje nivoa ekspresije odabranih gena u uparenim uzorcima inflamirane i neinflamirane mukoze intestinuma izvršeno je primenom metode real-time PCR. Rezultati ekspresione analize pokazali su značajno više nivoe ekspresije IL17A i IL17F u inflamiranoj mukozi intestinuma ZBC. Inflamirana mukoza ileuma u KB i mukoza kod UK pokazale su povišenu ekspresiju IL23A, dok su inflamirani uzorci ileuma kod KB imali povišen nivo TLR9. Nivo ekspresije ispitivanih gena bio je povezan sa fenotipom i težinom ZBC. Uočena je značajna razlika u nivou odnosa ekspresije IL17A/IL17F između bolesne i zdrave mukoze kod UK. Pokazano je da su IL17A, IL17F, IL23A i TLR9 značajni za nastanak i kliničku sliku ZBC. Međutim, ekspresioni profili ovih gena nisu isti kod različitih fenotipova KB i UK što može uticati na precizniju, molekularnu klasifikaciju ZBC i primenu personalizovanog pristupa u terapiji ovih bolesti.

Inflammatory bowel diseases (IBD) are chronic, idiopathic diseases that include Crohn's disease (CD) and ulcerative colitis (UC). IBD development is associated with disrupted immune response to the intestinal microflora in genetically susceptible hosts. The signaling interplay of Toll-like receptor 9 (TLR9), interleukin (IL) -23 and IL-17 in the pathogenesis of IBD has not been completly claryfied. The aim of this study was to investigate differences in IL17A, IL17F, IL23A, and TLR9 expression in paired inflamed and non-inflamed intestinal mucosa in patients with endoscopically active IBD. An additional goal was to associate the expression levels of these genes with the clinical parameters of CD and UC. Since the IL17A and IL17F ratio is important for the regulation of the inflammatory process, another aim was to evaluate the interrelation of their expression in inflamed and non-inflamed IBD mucosa. The study included 104 newly diagnosed IBD patients (50 CD, 54 UC). Expression analysis of selected genes was performed in paired samples of inflamed and non-inflamed mucosa of the intestinum by real-time PCR. Expression profile results showed significantly increased levels of IL17A and IL17F in inflamed IBD mucosa. Inlamed CD ileal and UC mucosa showed increased IL23A, while only inflamed CD ileal samples showed increased TLR9 levels. The examined genes expression level was related to the phenotype and severity of IBD. A significant difference was observed in the level of IL17A / IL17F expression ratio between inflamed and non-inflamed mucosa in the UC. We showed that IL17A, IL17F, IL23A and TLR9 are significant for IBD development and clinical presentation. However, the expression profiles of these genes are not the same for different CD and UC phenotypes, which may contribute to the more precise, molecular classification of IBD and personalized approach in the treatment of these diseases.

zapaljenske bolesti creva, Kronova bolest, ulcerozni kolitis, ekspresioni profil IL17A, IL17F, IL23A i TLR9 gena

inflammatory bowel disease, Crohn disease, ulcerative colitis, expresion profiling of IL17A, IL17F, IL23A, TLR9 gene

616.34-002:577.2(043.3)

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