Carrageenan-induced colonic inflammation is reduced in Bcl10 null mice and increased in IL-10-deficient mice

Mediators Inflamm. 2013;2013:397642. doi: 10.1155/2013/397642. Epub 2013 May 26.

Abstract

The common food additive carrageenan is a known activator of inflammation in mammalian tissues and stimulates both the canonical and noncanonical pathways of NF-κB activation. Exposure to low concentrations of carrageenan (10 μ 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-κB-inducing kinase (NIK), and phospho(Ser36)-IκBα 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-κB (RelA) activation, but without increase in RelB or phospho-Bcl10, and exogenous IL-10 inhibited only the canonical pathway of NF- κ 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • B-Cell CLL-Lymphoma 10 Protein
  • Carrageenan / toxicity*
  • Cell Line
  • Chemokine CCL2 / blood
  • Colon / drug effects*
  • Colon / immunology*
  • Colon / metabolism
  • Colon / pathology
  • Cytokines / blood
  • Enzyme-Linked Immunosorbent Assay
  • In Vitro Techniques
  • Inflammation / chemically induced*
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Interleukin-10 / deficiency
  • Interleukin-10 / metabolism*
  • Interleukin-6 / blood
  • Interleukin-8 / blood
  • Leukocyte L1 Antigen Complex / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • NF-kappa B / blood
  • Phosphorylation

Substances

  • Adaptor Proteins, Signal Transducing
  • B-Cell CLL-Lymphoma 10 Protein
  • Bcl10 protein, mouse
  • Chemokine CCL2
  • Cytokines
  • Interleukin-6
  • Interleukin-8
  • Leukocyte L1 Antigen Complex
  • NF-kappa B
  • Interleukin-10
  • Carrageenan