IL-1β stimulates IL-8 production, including prostaglandin E2 receptor EP4-triggered pathways, in synoviocyte MH7A cells

: Prostaglandin E2 (PGE2) is an important modulator of cytokine-driven inflammation. Using GeneChip analysis, we found that interleukin (IL)-1β induces the gene expression of PTGER4, which encodes the PGE2 receptor subtype EP4 (PGE2EP4). This subtype is one of four PGE2 receptors occurring in synoviocyte MH7A cells. Immunofluorescence microscopy revealed a corresponding upregulation in the production of PGE2EP4 protein in IL-1β-pretreated MH7A cells. PGE2 alone has no effect on IL-8 production, but in cells pretreated with IL-1β it markedly enhances IL-8 production. Moreover, a stimulatory effect of PGE2 on IL-8 production in the synoviocyte MH7A cells was observed. These results indicate that, in the synovial tissues of patients with rheumatoid arthritis, PGE2 stimulates the release of IL-8 from the fibroblastic cells classified as present, thereby exacerbating inflammation.