CHEMOKINES PRODUCED BY MESOTHELIAL CELLS - HUGRO-ALPHA, IP-10, MCP-1 AND RANTES

Recently we showed the in vivo relevance of chemokines in cases of bac terial peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. Mesothelial cells, the most numerous cells in the peritonea l cavity, are hypothesized to function as a main source of chemokine p roduction. We investigated the time-and dose-dependent expression patt erns of four chemokines by mesothelial cells at the mRNA and protein l evel in response to stimulation with physiological doses of proinflamm atory mediators that are present at the site of bacterial inflammation . Besides the chemokines huGRO-alpha (attractant for neutrophils), MCP -1 and RANTES (monocyte attractants), the expression and production of IP-10 was analysed. Mesothelial cells were cultured and stimulated wi th either IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) or IFN-g amma or combinations of these. The time-and dose-dependent mRNA expres sion of the chemokines was determined by Northern blot analysis and th e protein production by ELISA. It was concluded that mesothelial cells could indeed be triggered by the mentioned stimuli to induce mRNA and protein production (huGRO-alpha and IP-10) or to augment constitutive protein production (MCP-1). However, RANTES mRNA and protein producti on could only be induced in some cases and only in small amounts. The chemokine response of mesothelial cells was regulated differentially, depending on the stimulus and the chemokine measured. In distinct case s, combination of the stimuli led to synergy in mRNA expression and pr otein production. The presented in vitro data support our hypothesis t hat mesothelial cells in vivo are the main source of relevant chemokin es in response to proinflammatory mediators, suggesting an important r ole for mesothelial cells in host defence.