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Toll‐Like Receptors 1,2,4,6 expression in Human Fibroblast of the Large Intestine
Author(s) -
HeltonRieter Megann Kathleen,
Reaves Titus A,
LeBel David
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.977.12
Subject(s) - fibroblast , fibrosis , receptor , inflammation , biology , immunology , toll like receptor , cytokine , medicine , innate immune system , pathology , immune system , cell culture , biochemistry , genetics
Crohn's Disease (CD) is characterized by dysregulated intestinal inflammation with an unknown etiology. Intestinal fibrosis is a major patho‐physiological complication of CD with features that include an over production of collagen, excessive contraction of intestine tissue, and intestinal stricture. The subepithelial fibroblast is the cell type responsible for producing the increased collagen and therefore, the associated fibrosis. Despite these observations, the cause and progression of intestinal fibrosis in CD is not clearly defined. Interestingly, persistent intestinal fibrosis has been reported in Salmonella infections in mice. Given that toll‐like receptors (TLRs) likely modulate the response to this pathogen, we characterized the expression of TLRs 1, 2, 4, and 6; and a TLR‐2 associated protein termed Triggering Receptor Expressed on Myeloid Cells (TREM‐1) in human intestinal fibroblasts. Results revealed that fibroblast express TLR's 2, 4, 6, and TREM‐1, but minimal to no expression of TLR‐1. Fibroblasts exposed to interleukin‐6 ((IL‐6), inflammatory cytokine abundantly expressed in CD), revealed a pronounced reduction in expression of TLR‐6 when compared to TLRs 2, 4 and TREM‐1. Since activation and proliferation of fibroblasts is the key component of fibrogenesis, then excessive exposure to microbes may result in aberrant collagen production thereby initiating intestinal fibrosis.