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Prostacyclin and prostaglandin E 2 inhibit proinflammatory cytokine‐induced macrophage colony‐stimulating factor production in cultured human glomerular mesangial cells
Author(s) -
KITAHARA Masashi,
MORI Tetsuo
Publication year - 1997
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/j.1440-1797.1997.tb00239.x
Subject(s) - prostacyclin , endocrinology , proinflammatory cytokine , medicine , forskolin , cytokine , monocyte , tumor necrosis factor alpha , macrophage colony stimulating factor , prostaglandin e , prostaglandin e2 , mesangium , mesangial cell , prostaglandin , macrophage , inflammation , biology , glomerulonephritis , kidney , stimulation , biochemistry , in vitro
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 E 2 (PGE 2 ). 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 PGE 2 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 PGE 2 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 PGE 2 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.