Interleukin-6, but not the interleukin-6 receptor plays a role in recovery from dextran sodium sulfate-induced colitis

Sommer,Jan; Engelowski,Erika; Baran,Paul; Garbers,Christoph; Floss,Doreen  M.; Scheller,Jürgen

doi:10.3892/ijmm.2014.1825

Interleukin-6, but not the interleukin-6 receptor plays a role in recovery from dextran sodium sulfate-induced colitis

Authors:
- Jan Sommer
- Erika Engelowski
- Paul Baran
- Christoph Garbers
- Doreen M. Floss
- Jürgen Scheller
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Affiliations: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, D-40225 Düsseldorf, Germany, Institute of Biochemistry, Medical Faculty, Christian-Albrechts-University, D-24098 Kiel, Germany
Published online on: June 27, 2014 https://doi.org/10.3892/ijmm.2014.1825
Pages: 651-660
Copyright: © Sommer et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Interleukin (IL)-6-deficient, but not IL-6 receptor (IL-6R)‑deficient mice present with a delayed skin wound healing phenotype. Since IL-6 solely signals via the IL-6R and glycoprotein 130 (gp130), Il-6r-deficient mice are expected to exhibit a similar phenotype as Il-6-deficient mice. However, p28 (IL-30) and ciliary neurotrophic factor (CNTF) have been identified as additional low‑affinity ligands of the IL-6R/gp130/LIFR complex. IL-6 plays an inflammatory and regenerative role in inflammatory bowel disease (IBD). In the present study, we compared Il-6r-deficient mice with mice treated with neutralizing IL-6 monoclonal antibody (mAb) in a model of dextran sodium sulfate (DSS)-induced colitis. Our results, in agreement with those of previous reports, demonstrated that IL-6 mAbs slightly attenuated DSS-induced colitis during the regeneration phase. Il-6r-deficient mice and mice with tissue-specific deletion of the Il-6r in the myeloid cell lineage (LysMCre) with acute and chronic DSS-induced colitis were, however, indistinguishable from wild-type mice. Our data suggest that IL-6 and IL-6R have an additional role in colitis, apart from the IL-6/IL-6R classic and trans-signaling.

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