Observational Study
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World J Gastroenterol. Sep 14, 2014; 20(34): 12249-12259
Published online Sep 14, 2014. doi: 10.3748/wjg.v20.i34.12249
Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis
Sezin Günaltay, Nils Nyhlin, Ashok Kumar Kumawat, Curt Tysk, Johan Bohr, Olof Hultgren, Elisabeth Hultgren Hörnquist
Sezin Günaltay, Ashok Kumar Kumawat, Elisabeth Hultgren Hörnquist, Department of Biomedicine, School of Health and Medical Sciences, Örebro University, SE-701 82 Örebro, Sweden
Nils Nyhlin, Curt Tysk, Johan Bohr, Department of Medicine, Division of Gastroenterology, Örebro University Hospital, School of Health and Medical Sciences, Örebro University, SE-701 85 Örebro, Sweden
Olof Hultgren, Department of Microbiology and Immunology, Örebro University Hospital, SE-701 85 Örebro, Sweden
Author contributions: Günaltay S carried out the experiments, analyzed the data, and drafted the manuscript; Günaltay S and Kumawat AK prepared the patient biopsies; Nyhlin N, Bohr J and Tysk C recruited the patients and performed the colonoscopies; Günaltay S, Hultgren-Hörnquist E, Hultgren O and Nyhlin N participated in the creation of the study design, coordination, and data analysis; Hultgren Hörnquist E and Hultgren O participated in finalization of the study design and of the manuscript; all authors read and approved the final manuscript.
Supported by Research Committee of Örebro County Council; Sezin Günaltay´s salary is covered by a grant from Örebro University
Correspondence to: Sezin Günaltay, MSc, Department of Biomedicine, School of Health and Medical Sciences, Örebro University, SE-701 82 Örebro, Sweden. sezin.gunaltay@oru.se
Telephone: +46-19-302192 Fax: +46-19-6026650
Received: October 23, 2013
Revised: February 14, 2014
Accepted: April 30, 2014
Published online: September 14, 2014
Abstract

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-1 receptor-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 = 0.01 and 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.

Keywords: Interleukin-37, MicroRNA, Lymphocytic colitis, Collagenous colitis, Ulcerative colitis

Core tip: Epithelial destruction is observed in both microscopic and ulcerative colitis, likely resulting in enhanced contact between gut microbiota and Toll-like receptors (TLRs), which do not normally face the lumen. Insufficiently regulated TLR signaling may result in chronic inflammation. In this study, we analyzed several important regulatory molecules of TLR signaling: interleukin-1 receptor-associated kinase (IRAK)-2, IRAK-M, interleukin (IL)-37, microRNA (miR)-146a, miR-155, and miR-21. A possible association between the regulatory effects of IRAK-M and miR-146a was revealed in both diseases. This novel analysis of miR-155 and miR-21 in microscopic and ulcerative colitis revealed different expressions in active disease and remission.