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Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis
Örebro universitet, Institutionen för hälsovetenskap och medicin.ORCID-id: 0000-0002-9635-0341
Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.ORCID-id: 0000-0002-0942-0816
Örebro universitet, Institutionen för hälsovetenskap och medicin.ORCID-id: 0000-0002-2244-9816
Region Örebro län. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.ORCID-id: 0000-0003-2191-9625
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2014 (Engelska)Ingår i: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, nr 34, s. 12249-12259Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Ort, förlag, år, upplaga, sidor
WJG Press , 2014. Vol. 20, nr 34, s. 12249-12259
Nyckelord [en]
Interleukin-37, MicroRNA, Lymphocytic colitis, Collagenous colitis, Ulcerative colitis
Nationell ämneskategori
Gastroenterologi
Identifikatorer
URN: urn:nbn:se:oru:diva-37676DOI: 10.3748/wjg.v20.i34.12249ISI: 000341719100033Scopus ID: 2-s2.0-84909606787OAI: oai:DiVA.org:oru-37676DiVA, id: diva2:754874
Anmärkning

Funding Agencies:

Research Committee of Örebro County Council

Örebro University

Tillgänglig från: 2014-10-13 Skapad: 2014-10-13 Senast uppdaterad: 2019-03-26Bibliografiskt granskad
Ingår i avhandling
1. Dysregulated mucosal immune responses in microscopic colitis patients
Öppna denna publikation i ny flik eller fönster >>Dysregulated mucosal immune responses in microscopic colitis patients
2016 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC) is a common cause of chronic watery diarrhea. The diagnosis relies on typical histopathological changes observed upon microscopic examination. The studies in this thesis investigated innate and adaptive immune responses in the colonic mucosa of MC patients, also comparing patients with active disease (CC and LC) and histopathologically in remission (CC/LC-HR). We first analyzed expression of interleukin-1/Toll-like receptor (IL-1/TLR) signaling regulators in MC patients (Paper I). Our results showed enhanced IRAK-M, microRNA-146a, -155 and -21 expressions, whereas IL-37 gene expression was reduced in CC and LC patients as compared to non-inflamed controls. These results suggest different pathophysiological mechanisms in MC patients. The mixed inflammatory cell infiltrations seen in the lamina propria of MC patients might be a result of dysregulated expression of chemotactic mediators. In Paper II, we showed that MC patients display mainly an increased expression of chemokines and chemokine receptors in active disease as compared to noninflamed controls. In Paper III, we examined if the decreased IL-37 expression seen in Paper I could mediate the upregulation of chemokines seen in Paper II. We showed that a relatively small reduction in the ability of epithelial cells to produce IL-37 results in mainly increased chemokine expressions in a pattern similar to the findings in Paper II. In order to understand the nature of infiltrating T cells commonly observed in MC patients, we analyzed the T cell receptor (TCR) β chains in colonic biopsies of MC patients (Paper IV). Our results showed significant differences in TCRβ repertoire, which suggests selectively expanded T cell clones in active MC and histopathologically in remission patients. Altogether, these results i) increase the knowledge of MC pathogenesis by showing changes in TLR signaling regulators, enhanced chemokine and their receptor expressions involved in a mixed immune cell infiltrations and selectively expanded T cell clones in CC and LC patients, as well as in histopathological remission ii) might potentially increase the possibility of more target-specific therapies based on IL-37 induction, chemokines or chemokine receptor inhibitions, or hindering T cell infiltration according to TCR clonality.

Ort, förlag, år, upplaga, sidor
Örebro: Örebro university, 2016. s. 102
Serie
Örebro Studies in Medicine, ISSN 1652-4063 ; 132
Nyckelord
Microscopic colitis, collagenous colitis, lymphocytic colitis, TLR, chemokine, chemokine receptor, IL-37, TCR
Nationell ämneskategori
Immunologi inom det medicinska området Annan medicinsk grundvetenskap
Forskningsämne
Immunologi; Biomedicin
Identifikatorer
urn:nbn:se:oru:diva-47390 (URN)978-91-7529-118-5 (ISBN)
Disputation
2016-03-04, Campus USÖ, Örebro universitet, hörsal C2, Södra Grev Rosengatan, Örebro, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2016-01-13 Skapad: 2016-01-13 Senast uppdaterad: 2018-01-10Bibliografiskt granskad

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Günaltay, SezinNyhlin, NilsKumawat, Ashok KumarTysk, CurtBohr, JohanHultgren, OlofHultgren-Hörnquist, Elisabeth

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Günaltay, SezinNyhlin, NilsKumawat, Ashok KumarTysk, CurtBohr, JohanHultgren, OlofHultgren-Hörnquist, Elisabeth
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Institutionen för hälsovetenskap och medicinRegion Örebro länInstitutionen för läkarutbildning
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