Prostacyclin and prostaglandin E2inhibit proinflammatory cytokine-induced macrophage colony-stimulating factor production in cultured human glomerular mesangial cells

Abstract

Summary: Monocyte/macrophages within the mesangium plays some important roles in the progression of renal glomerular injury in which prostanoids exert a broad range of actions. We have examined the production of macrophage colony-stimulating factor (M-CSF), a monocyte-specific cytokine, by human glomerular mesangial cells (MC) and its regulation by prostacyclin and prostaglandin E2 (PGE2). the MCSF production by MC under non-stimulatory conditions was below detectable levels by ELISA, and was also at a trace level in the steady-state M-CSF mRNA expression. Proinflammatory cytokines, interleukin-1β (IL-1β) or tumour necrosis factor-α (TNF-α) induced the M-CSF production in the protein and mRNA levels. Both beraprost, a stable analogue of prostacyclin, and PGE2 attenuated the IL-1β- or TNF-α-driven M-CSF production. Indomethacin, a non-selective cyclooxygenase inhibitor, enhanced the IL-1β- or TNF at-induced M-CSF production. Beraprost and PGE2 showed similar inhibitory effects in the presence of indomethacin. Forskolin, a direct activator of adenylate cyclase, and dibutyryl cAMP decreased the M-CSF production. These results indicate that: (i) human MC have capacity to produce M-CSF; (ii) exogenous prostacyclin and PGE2 downregulate the IL-1β- or TNF-α-driven M-CSF production possibly by an increase of intracellular cAMP; and (iii) endogenous prostanoids can exert on the M-CSF production.