Chemokines produced by mesothelial cells: huGRO-α, IP-10, MCP-1 and RANTES

Abstract

Recently we showed the in vivo relevance of chemokines in cases of bacterial peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. Mesothelial cells, the most numerous cells in the peritoneal cavity, are hypothesized to function as a main source of chemokine production. We investigated the time- and dose-dependent expression patterns of four chemokines by mesothelial cells at the mRNA and protein level in response to stimulation with physiological doses of proinflammatory 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 with either IL-1beta, tumour necrosis factor-alpha (TNF-alpha) or IFN-gamma or combinations of these. The time- and dose-dependent mRNA expression of the chemokines was determined by Northern blot analysis and the 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 production 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 cases, combination of the stimuli led to synergy in mRNA expression and protein production. The presented in vitro data support our hypothesis that mesothelial cells in vivo are the main source of relevant chemokines in response to proinflammatory mediators, suggesting an important role for mesothelial cells in host defence.

IL-17 Stimulates Intraperitoneal Neutrophil Infiltration Through the Release of GROα Chemokine from Mesothelial Cells

“…We have therefore concentrated on peritoneal mesothelial cells. The peritoneal mesothelium is a recognized source of chemotactic activity in the peritoneum (32,(52)(53)(54), and it has been demonstrated that on appropriate stimulation human mesothelial cells are capable of generating GRO␣, a homologue of KC (55). The presence of IL-17R mRNA in HPMC was demonstrated by RT-PCR and confirmed the ubiquitous nature of IL-17R distribution (20,21).…”

Differential Regulation of Chemokine Production in Human Peritoneal Mesothelial Cells: IFN-γ Controls Neutrophil Migration Across the Mesothelium In Vitro and In Vivo

“…Similarly, IFN-␥-and IFN-␤-inhibited neutrophil-specific chemokine production (IL-8, ENA-78) in LPS or IL-1␤ stimulated monocytes (37). In contrast, Yasumoto et al (39) reported synergistic up-regulation of IL-8 production with the combination of IFN-␥ and TNF-␣ in a human gastric cancer cell line, and in HPMC, Visser et al (8) described no effect of IFN-␥ on basal or IL-1␤-or TNF-␣-induced IL-8 production. Our findings that the potential of IFN-␥ to regulate IL-8 production was critically dependent on the dose of IL-1␤ or TNF-␣ used, with inhibition evident at lower doses but stimulation present at higher ones, may in part explain the observed differences in the published literature.…”

“…8). Studies that use a transwell culture systems, in which polarized cultures of HPMC are established on porous inserts, have demonstrated that chemokine secretion by IL-1␤-or TNF-␣-activated HPMC is directional, with Ͼ80% of the chemokine secreted apically, resulting in the formation of a chemotactic gradient across the cell monolayer.…”

Abnormal regulation of chemokine TECK and its receptor CCR9 in the endometriotic milieu is involved in pathogenesis of endometriosis by way of enhancing invasiveness of endometrial stromal cells

“…Chemokines have the ability to attract and activate inflammatory cells. 3 It is increasingly clear that some chemokines play an important role in many physiological and pathological situations, such as ovulation, menstruation, implantation, cervical ripening, pre-term labor and endometriosis. 4,5 Chemokine C receptor 9 (CCR9) is expressed mainly on immature T cells, such as double-positive (DP) T cells or gut-associated T cells, 6 which makes CCR9 a valuable receptor for T-cell development and tissue-specific homing.…”

“…Dioxin (2,3,7, TCDD), an air pollutant, and estrogen also appear to be involved in endometriosis. Both endometrial stromal cells (ESCs) and the combination of 17b-estradiol and TCDD increase the secretion of TECK in the endometriosis-associated cells and promote the invasiveness of ESCs by increasing expression of matrix metalloproteinase (MMP)-2 and MMP-9.…”