title: Role of IL-10 in the crossregulation of prostaglandins and cytokines in monocytes.
abstract: In the present study we have focused mainly on the role of IL (interleukin)-10 in the crossregulation of prostaglandins and cytokines in human monocytes. We first determined the effects of tumor necrosis factor-alpha (TNF-alpha) and IL-10 on monocyte prostaglandin E2 (PGE2) production. Unstimulated monocytes constitutively produced a small but significant amount of PGE2 in the culture supernatants. Both TNF-alpha and lipopolysaccharide (LPS) caused a remarkable increase in monocyte PGE2 production. On the other hand, IL-10 alone was without effect on constitutive PGE2 production but drastically inhibited LPS-induced PGE2 production in monocytes. Moreover, this inhibitory effect of IL-10 was not simply attributable to its inhibition of TNF-alpha production in LPS-stimulated monocytes. Next, we determined the effect of PGE2 on TNF-alpha mRNA expression in monocytes. Treatment of monocytes with or without PGE2 showed no detectable TNF-alpha mRNA. Activation of monocytes by LPS resulted in a remarkable accumulation of TNF-alpha mRNA and PGE2 efficiently inhibited this expression. Finally, we determined the effect of PGE2 on IL-10 mRNA expression in monocytes. Similar to TNF-alpha mRNA, unstimulated monocytes showed no detectable IL-10 mRNA. Interestingly, PGE2 alone drastically induced IL-10 mRNA. Besides, activation of monocytes by LPS resulted in a remarkable accumulation of IL-10 mRNA, and PGE2 further enhanced this expression. These results indicate that TNF-alpha and PGE2 are key molecules for the induction of IL-10 in monocytes, and that IL-10, in turn, plays a crucial role in terminating the inflammatory cascade via downregulation of production of proinflammatory molecules including TNF-alpha and PGE2.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Niho
authors.forename: H
authors.initials: H
authors.lastname: Niiro
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Nakashima
authors.forename: T
authors.initials: T
authors.lastname: Otsuka
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D011453:Prostaglandins / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015232:Dinoprostone