Role of intestinal fibroblasts in inflammation across the intestinal epithelium (488.10)

Abstract

Fibroblasts are mesenchymal cells that produce extracellular matrix (ECM) proteins and play a major role in tissue repair (i.e., resolution of inflammation). Fibroblasts can affect cells in the local environment through the release of cytokines, growth and differentiation factors. CD36 is a membrane‐bound and scavenger receptor that is an indicator of inflammation and interacts with TLR‐2, 4, and 6. We investigated intestinal fibroblasts for expression of immune receptors and for a role of CD36 in intestinal inflammation using fibroblasts exposed to a series of cytokines. Analysis of supernatants revealed the presence of IL‐8 (potent chemoattractant for polymorphonuclear leukocytes, (PMN)) in IL‐6 treated normal and CD36‐deficient fibroblasts. However, results reveal a statistically significant reduction in PMN migration using IL‐6 treated CD36‐deficient cells. Kinase inhibitor experiments reveal that PI3 kinase pathway may be involved in the lL‐6 mediated release of IL‐8 from fibroblasts. Fibroblasts exposed to IL‐8 have been reported to display a myofibroblast‐like phenotype. Differences in cell adhesion and migration were also revealed using CD36‐deficient fibroblasts. Results show that fibroblasts can play a major role in the inflammatory responses in the intestine, PI3 kinase may be involved, and highlight CD36 as a target‐receptor that may modulate the inflammatory responses of fibroblasts.Grant Funding Source: NSF‐RII, NIH/NIDDK 5T35 DK007431