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Carrageenan-Induced Colonic Inflammation Is Reduced in Bcl10 Null Mice and Increased in IL-10-Deficient Mice

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journal contribution
posted on 19.02.2014, 00:00 by Sumit Bhattacharyya, Liquan Xue, Suzanne Devkota, Eugene Chang, Stephan Morris, Joanne K. Tobacman
The common food additive carrageenan is a known activator of inflammation in mammalian tissues and stimulates both the canonical and noncanonical pathways of NF-kappa B activation. Exposure to low concentrations of carrageenan (10 mu g/mL in the water supply) has produced glucose intolerance, insulin resistance, and impaired insulin signaling in C57BL/6 mice. B-cell leukemia/lymphoma 10 (Bcl10) is a mediator of inflammatory signals from Toll-like receptor (TLR) 4 in myeloid and epithelial cells. Since the TLR4 signaling pathway is activated in diabetes and by carrageenan, we addressed systemic and intestinal inflammatory responses following carrageenan exposure in Bcl10 wild type, heterozygous, and null mice. Fecal calprotectin and circulating keratinocyte chemokine (KC), nuclear RelA and RelB, phospho(Thr559)-NF-kappa B-inducing kinase (NIK), and phospho(Ser36)-I kappa B alpha in the colonic epithelial cells were significantly less (P < 0.001) in the carrageenan-treated Bcl10 null mice than in controls. IL-10-deficient mice exposed to carrageenan in a germ-free environment showed an increase in activation of the canonical pathway of NF-kappa B (RelA) activation, but without increase in RelB or phospho-Bcl10, and exogenous IL-10 inhibited only the canonical pathway of NF-kappa B activation in cultured colonic cells. These findings demonstrate a Bcl10 requirement for maximum development of carrageenan-induced inflammation and lack of complete suppression by IL-10 of carrageenan-induced inflammation.

Funding

Funding was by Merit Review from the Veteran’s Administration to J. K. Tobacman and DDRCC (DK42086) and UH3 DK083993 to E. Chang for the support of the gnotobiotic facility.

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Publisher Statement

Copyright © 2013 Sumit Bhattacharyya et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Publisher

Hindawi Publishing Corporation

Language

en_US

issn

0962-9351

Issue date

01/05/2013

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