GM-CSF, IL-1α, IL-β, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 gene expression and cytokine production in human duodenal fibroblasts stimulated with lipopolysaccharide, IL-1α and TNF-α

Abstract

SUMMARY The role of mucosal fibroblasts in intestinal inflammatory reactions is not known. In this study, we demonstrate that fibroblasts grown from histologically normal human duodenal biopsy tissues expressed mRNA genes for granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). IL‐lα, IL‐1β, IL‐6, IL‐8, IL‐10, intercellular adhesion molecule‐I (ICAM‐I) and vascular cell adhesion molecule‐1 (VCAM‐i) when stimulated with lipopolysaccharide (LPS) or IL‐1α. The increased mRNA expression of GM‐CSF, IL‐1α IL‐1β IL‐6 and IL‐α in response to IL‐1α and LPS stimulation was time‐ and dose‐dependent. In contrast. IL‐10 was weakly expressed when fibroblasts were stimulated with LPS. IL‐1α or tumour necrosis factor‐alpha (TNF‐α), but the expression was enhanced in the presence of cycloheximide combined with optimal concentrations of LPS. IL‐1α or TNF‐α. IL‐1α was a more potent stimulator than LPS for GM‐CSF. IL‐6, IL‐8 and I L‐10 expression, but not for IL‐1α and IL‐1β. Increased GM‐CSF. lL‐6 and IL‐8 gene expression was associated with the production of cytokine proteins in culture supernatant, but IL‐1α and IL‐1bL remained undetectable. Dexamethasone suppressed both gene expression and protein production of GM‐CSF. IL‐6 and IL‐8 when fibroblasts were exposed to IL‐1α. TNF‐α stimulated the release of GM‐CSF. IL‐6 and IL‐8 and, combined with IL‐1α. cytokine production was enhanced synergistically. Finally, both LPS and IL‐1ã up‐regulated ICAM‐I and VCAM‐1 gene expression. These findings implicate duodenal fibroblasts in the initiation and/or regulation of intestinal inflammation.

Mucosal IL-10 and TGF-β play crucial roles in preventing LPS-driven, IFN-γ–mediated epithelial damage in human colon explants

“…In addition, we demonstrate in this study that IL-10 was not only produced, but also secreted, in the culture medium of mucosa explant cultures. The current prevailing concept in the literature is that IL-10 is synthesized in the human intestinal mucosa mainly by immune cellsincluding regulatory T cells, B cells, macrophages, and dendritic cells -and also by fibroblasts and epithelial cells (15,(20)(21)(22), a distribution analog to that previously reported in the mouse intestinal mucosa (23)(24)(25)(26)(27)(28)(29). Here we show that IL-10 was constitutively synthesized and secreted in the human colonic mucosa by resident cells, including epithelial cells.…”

Cancer cell-derived IL-1α induces IL-8 release in endothelial cells

“…Among the 8,400 genes tested, the expression level of four genes, IL-8, ICAM-1, SOD-2, and GABAR A6, increased more than fourfold. ProinXammatory cytokines, IL-1 , IL-1 and TNF-were reported to induce IL-8, ICAM-1 and SOD-2 in various cells (Pang et al 1994;Nakata et al 1993;Ono et al 1992;Chokki et al 2006). In our study, IL-8 and ICAM-1 induction caused by IL-1 in SNUC5 CM was conWrmed in neutralization and depletion assays with an antibody speciWc to IL-1 ( Fig.…”

“…IL-1 in conditioned medium of SNUC5 directly induced over-expression and release of IL-8 in HUVECs ProinXammatory cytokines, IL-1 , IL-1 and TNF-have been reported to induce IL-8 over-expression (Matsushima and Oppenheim 1989;Pang et al 1994). In order to identify the molecule inducing IL-8 over-expression and release from HUVECs, we performed a neutralization assay using blocking antibodies against IL-1 , IL-1 and TNF-.…”

A probabilistic approach for links between rheumatic diseases and weather

“…Mast cell results in rapid release of TNF-alpha, inducing IL-6 in infiltrating mononuclear cells 11. TNF-alpha of mast cell origin may be a crucial factor in upregulating IL-6 [14]. IL-1 and TNF-alpha are pro-inflammatory mediators at several joint cells including synovial fibroblast, macrophages, and chondrocytes.…”