3 fold increase in COX 2 gene expression. In the pres ence of laminarin there was a lower, 1. 6 0. 3 fold, but signif icant increase in COX 2 gene expression when synovial fibroblasts were infected with C. albicans. This 20% decrease in COX 2 gene expression by laminarin was statisti cally significantly. COX 2 gene expression was significantly upregulated when synovial fibrob lasts and C. albicans were co cultured in different trans well chambers. This indicates that direct contact may have only a minor contribution to the elevation of COX 2 gene expression seen when synovial fibroblasts are infected with C. albicans. Discussion The present study has demonstrated that synovial fibroblast expression of COX 2, under the control of ERK12, is induced following C. albicans infection.
Upregulation of COX 2 is associated with NFB activation and appears to be more prominent in synovial fibroblasts adjacent to fungal colonies. The finding that ERK12 phosphorylation occurs on exposure of synovial fibroblasts to C. albicans is consistent with obser vations of interactions of C. albicans with inflammatory and epithelial cells. selleck Phagocytosis of C. albicans by macrophages results in ERK phosphorylation and TNF production by monocytes exposed to C. albicans is ERK dependent. TLR2 appears to be the major receptor mediating PGE2 pro duction by mouse macrophages in response to C. albicans. C. albicans increases COX 2 expression in HeLa cells with roles for both TLR2 and TLR4 being identified. Sim ilar mechanisms are likely to be involved in the induction of COX 2 and PGE2 production in the current study.
Toll like receptors have been shown to be involved in synovial inflammation i was reading this in a wide range of inflammatory joint diseases including rheumatoid arthritis, Lyme arthritis, and streptococcal cell wall induced arthritis. TLR signaling is also likely to be involved in mediating proinflammatory responses and subsequent tissue destruction in fungal arthri tis. The basic cell wall structure of C. albicans consists of a lin ear glucan backbone from which there are covalently attached branches of additional glucan and mannoproteins. Mannoproteins, highly antigenic proteins with large numbers of mannose groups attached have been shown to induce pro inflammatory cytokine production in murine macrophages and human mononuclear cells.
Mannose containing molecular patterns are also strong inducers of COX 2 expression and PGE2 production in human macrophages. TLR have important roles in the induction of cytokines by fungi with TLR4 recognition of O linked mannosyl residues present in the C. albicans cell wall are thought to be particularly important. Phospholipomannan, present in the cell surface of C. albicans, has been shown to be recognized by TLR2. Cytokine induction by C.