Interleukin 4 downregulates cell growth and prostaglandin release of human mesangial cells.
Several clinical studies have proposed that a T cell derived cytokine IL-4 is operative in glomerulonephritis; however, its biological activities on renal cells have not been investigated. To elucidate its possible role in glomerulonephritis, we have examined whether IL-4 has effect on cell growth and prostaglandins synthesis using cultured mesangial cells (MC). IL-4 dose-dependently suppressed DNA synthesis and cell proliferation. IL-4 (10 ng/ml) alone did not affect prostaglandin E2 (PGE2) synthesis by mesangial cells, though, it inhibited IL-1 alpha- and TNF alpha-stimulated PGE2 synthesis by 48% and 81%, respectively. Comparable inhibition was observed on the conversion of exogenous arachidonic acid to PGs by IL-1-stimulated cells, suggesting IL-4 down regulates PG endoperoxide synthase activity. These results demonstrated that IL-4 is antagonistic to inflammatory cytokines upon PG synthesis as well as anti-mitogenic with MC.
Nakazato
Y
Y
Health Center, School of Medicine, Keio University, Tokyo, Japan.
Okada
H
H
Sato
A
A
Iwaita
Y
Y
Hayashida
T
T
Hayashi
M
M
Suzuki
H
H
Saruta
T
T
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D016718:Arachidonic Acid / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005921:Glomerulonephritis / Q000503:physiopathology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D007700:Kinetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D011453:Prostaglandins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D007371:Interferon-gamma; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone