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FPR1 and Activation of Intestinal Fibroblasts
Author(s) -
Reaves Titus A.,
AndersonThomas Meghan,
Nillas Andrea,
Lecher Mackenzie
Publication year - 2016
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.30.1_supplement.57.10
Subject(s) - myofibroblast , microbiology and biotechnology , downregulation and upregulation , fibrosis , wound healing , fibroblast , lipopolysaccharide , connective tissue , chemistry , receptor , inflammation , cancer research , mesenchymal stem cell , flow cytometry , hepatic stellate cell , immunology , biology , medicine , pathology , endocrinology , biochemistry , in vitro , gene
Fibroblasts are mesenchymal cells that produced the connective tissue consisting of collagens, laminins, and proteoglycans. Myofibroblasts are activated fibroblasts that express α‐smooth muscle actin and contract during wound healing. If activation continues, myofibroblasts become over‐activated and intestinal fibrosis (excessive and dysregulated collagen production that affects the function of the intestine) may result. Despite this information, the molecular events of fibrosis are not completely understood. We have shown that fibroblasts express the N α ‐formyl‐L‐methionyl‐L‐phenyalanine receptor (FPR1), which is a G‐protein coupled receptor that regulates the leukocyte response to bacterial formylated peptides. We initially exposed intestinal fibroblasts to a variety of inflammatory mediators that include lipopolysaccharide (LPS), IL‐6, and IL‐8. Interestingly, LPS treatment resulted substantial upregulation of FPR1, while IL‐8 treatment resulted in a substantial down‐regulation of FPR1. Using Flow Cytometry, similar results were obtained. We examined whether constitutive activation of the FPR1 (and inhibitors) resulted in the over‐activation of myofibroblasts and ultimate release of excessive and dysregulated collagen. Studies revealed that reducing FPR1 exacerbates the inflammatory response of fibroblasts. Taken together, the FPR1 appears to modulate the activation of fibroblasts. Down‐regulation of the FPR1 may lead to a better understanding the fibrotic response and better treatments of dysregulated inflammatory conditions involving fibroblasts. Support or Funding Information National Science Foundation RII