Interleukin-13 is a more potent inhibitor of the expression of inducible nitric oxide synthase in smooth muscle cells than in macrophages: a comparison with interleukin-4 and interleukin-10.
This study compares the effects of interleukin (IL)-13, a cytokine with anti-inflammatory properties, with those of IL-4 or IL-10 on the expression of inducible nitric oxide synthase (iNOS) protein and activity in 1) a murine macrophage cell line (J774.2) activated with lipopolysaccharide (LPS) and 2) rat aortic smooth muscle cells (RASM) activated with LPS plus interferon-gamma. Pretreatment of macrophages with IL-4 or IL-13 caused a similar, concentration-dependent inhibition of the formation of nitrite and the expression of iNOS protein elicited by LPS. In contrast, IL-13 was a much more potent inhibitor of the formation of nitrite and the expression of iNOS protein in activated RASM than IL-4. IL-10 caused only a small, but significant, inhibition of the nitrite formation induced by LPS in macrophages and RASM. Pretreatment of J774.2 macrophages, but not of RASM, with the phosphatidylinositol-3-kinase inhibitor, wortmannin (10-100 nM), attenuated the inhibition by either IL-13 or IL-4 of the LPS-induced increase in nitrite in a dose-related fashion. Thus, IL-13 is more potent than IL-4 in preventing the expression of iNOS protein and activity in activated RASM, whereas IL-13 and IL-4 are equipotent in inhibiting the expression of iNOS protein and activity in J774.2 macrophages.
Ruetten
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William Harvey Research Institute, St. Bartholomew's, London, United Kingdom.
Thiemermann
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D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000037:antagonists & inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects; D000077191:Wortmannin
D000276:Adjuvants, Immunologic; D000730:Androstadienes; D004731:Endotoxins; D004791:Enzyme Inhibitors; D018793:Interleukin-13; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009573:Nitrites; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; D000077191:Wortmannin