Heme oxygenase 1 expression induced by IL-10 requires STAT-3 and phosphoinositol-3 kinase and is inhibited by lipopolysaccharide.
Heme-oxygenase 1 (HO-1) is a stress-response protein with anti-inflammatory activity. This study has examined the regulation of HO-1 expression by the anti-inflammatory factor, interleukin (IL)-10 and whether HO-1 could account for the function of the cytokine. IL-10-induced expression of HO-1 required the activation of signal transducer and activator of transcription (STAT)-3 but not p38 mitogen-activated protein kinase. However, expression of HO-1 also required the activation of the phosphatidylinositol-3 kinase pathway, a signaling mechanism not required for the anti-inflammatory activity of IL-10. Moreover, induction of HO-1 expression was not restricted to IL-10, as IL-6, a cytokine known to activate STAT-3, could also induce the protein. In human macrophages, lipopolysaccharide inhibited HO-1 expression induced by IL-10. Also, inhibition of HO-1 activity by the specific inhibitor zinc-II-protoporphyrin-IX had no effect on the anti-inflammatory function of IL-10. In summary, although IL-10 does regulate HO-1 expression, it does not appear to play a significant role in the anti-inflammatory activity of the cytokine.
Ricchetti
Giuseppe A
GA
Kennedy Institute of Rheumatology Division, Imperial College London, Hammersmith, UK.
Williams
Lynn M
LM
Foxwell
Brian M J
BM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D025461:Feedback, Physiological / Q000187:drug effects / Q000276:immunology; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism*; D011524:Protoporphyrins / Q000494:pharmacology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011524:Protoporphyrins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D016753:Interleukin-10; C017803:zinc protoporphyrin; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D019869:Phosphatidylinositol 3-Kinases