Inhibition of p38 MAP kinase decreases the production of MCP-1 and IL-8 in endometrial stromal cells

Abstract

Mitogen-activated protein kinase (MAPK) pathway is one of the most ubiquotus signaling pathways. This pathway is activated by a variety of cellular stimuli and regulates numerous physiological processes. It has been proposed that p38 MAPK functions in the regulation of cytokine and chemokine expression. Given the role of p38 MAPK in cellular inflammatory responses, we aimed to determine whether p38 MAPK pathway is involved in the production of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) in endometrial stromal cells. A prospective in vitro study to assess the effect of p38 MAPK inhibition on IL-8 and MCP-1 expression in endometrial stromal cells. Endometrial tissues were obtained from women undergoing surgery for benign gynecologic conditions. Endometrial stromal cells were isolated and cultured in Ham’s F-12: DME medium that contained 10% fetal bovine serum, and grown to confluence. Experiments were performed after incubating cells in serum-free, phenol red-free medium for 24 h. Statistical analysis of the data was performed using ANOVA. Cells were treated for 24 h with a specific p38 MAPK inhibitor, SB203580 (10 μM) or with vehicle (control), and supernatants were collected. IL-8 and MCP-1 levels in culture media were quantified using a specific ELISA for each chemokine. Treatment of cells with p38 MAPK inhibitor resulted in a 37±2% (mean±SEM; p<0.001) decrease in IL-8 levels and a 29±2% (mean±SEM; p=0.003) decrease in MCP-1 levels. Inhibition of p38 MAPK signaling pathway significantly inhibited IL-8 and MCP-1 production in endometrial stromal cells. Therefore, we propose that IL-8 and MCP-1 expression in these cells, is at least partially regulated through p38 MAPK pathway. We speculate that this pathway may be involved in the pathogenesis of endometriosis, a proinflammatory disease where high levels of these chemokines are observed.