Reduced IL-37 Production Increases Spontaneous Chemokine Expressions in Colon Epithelial CellsReportar como inadecuado




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Digestive Diseases and Sciences

, Volume 62, Issue 5, pp 1204–1215

First Online: 02 January 2017Received: 27 July 2016Accepted: 16 December 2016DOI: 10.1007-s10620-016-4422-9

Cite this article as: Günaltay, S., Ghiboub, M., Hultgren, O. et al. Dig Dis Sci 2017 62: 1204. doi:10.1007-s10620-016-4422-9

Abstract

Background and AimMicroscopic colitis, comprising collagenous colitis and lymphocytic colitis, is a common cause of chronic diarrhea. Previously, we showed enhanced chemokine productions in microscopic colitis patients, indicating dysregulated immune cell chemotaxis in the immunopathogenesis. We also showed decreased mRNA of IL-37, mainly regarded as an anti-inflammatory cytokine, in the colonic mucosa of these patients, potentially an important factor for the chronicity of the colitis. Our aim in this study was to understand the possible role of IL-37 in chemokine production using a cell line model.

MethodsA colon epithelial cell line, T84, was stimulated with the TLR5 ligand flagellin. IL-37 protein production was reduced 20% using the CRISPR-Cas9 system, and the changes in chemokine mRNA and protein expressions were compared to cells transfected with empty plasmid.

ResultsThe 20% reduction in IL-37 protein levels spontaneously increased CCL5, CXCL8, CXCL10, and CXCL11 mRNA and protein expressions. CCL2 mRNA and protein levels were enhanced upon TLR5 stimulation. CCL3, CCL20, and CX3CL1 mRNA expressions were increased either spontaneously or following TLR5 stimulation, whereas CCL4 and CCL22 mRNA expressions were significantly decreased.

ConclusionsEven a minor decrease in the ability of colon epithelial cells to produce IL-37 results in altered chemokine expression, mainly an increase in the production of several chemokines. Our results indicate that a decreased IL-37 expression by colon epithelial cells may be an important factor for increasing the recruitment of immune cells and subsequently developing microscopic colitis.

KeywordsIL-37 Chemokines CRISPR-Cas9 



Autor: Sezin Günaltay - Mohammed Ghiboub - Olof Hultgren - Elisabeth Hultgren Hörnquist

Fuente: https://link.springer.com/







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