Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis

AIM:To investigate Toll-like receptor(TLR)signaling regulators in microscopic and ulcerative colitis patients.METHODS:Total RNA and microRNA were isolated from fresh frozen colonic biopsies of non-inflamed controls and patients with active or in-remission collagenous colitis(CC),lymphocytic colitis(LC),or ulcerative colitis(UC).We compared expressions of interleukin-1receptor-associated kinase(IRAK)-2,IRAK-M,interleukin(IL)-37,microRNA(miR)-146a,miR-155,and miR-21 using quantitative real time reverse transcription polymerase chain reaction.RESULTS:IRAK-M expression was increased in LC patients with active disease in histopathological remission(LC-HR;P=0.02)and UC patients(P=0.01),but no differences in IRAK-2 expression were detected compared to controls.miR-146a,-155 and-21 expressions were increased in LC-HR(P=0.04,0.07,and 0.004)and UC(P=0.02,0.04 and 0.03)patients.miR-146a and miR-21 expressions were significantly enhanced in UC patients compared to UC remission(UC-R;P=0.01and 0.04).Likewise,active CC patients showed significantly increased expression of miR-155(P=0.003)and miR-21(P=0.006).IL-37 expression was decreased in both CC(P=0.03)and LC(P=0.04)patients with a similar trend in UC patients but not statistically significant,whilst it was increased in UC-R patients compared to controls(P=0.02)and active UC(P=0.001).CONCLUSION:The identification of differentially expressed miRNAs,IL-37,and IRAK-M suggests different pathophysiologic mechanisms in various disease stages in LC,CC,and UC.

Fecal stream diversion and mucosal cytokine levels in collagenous colitis:A case report

In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs:loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin(IL)-1β,IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-γ, IL-4, IL-5,IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction,the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis.