Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents / immunology
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Anti-Inflammatory Agents / metabolism*
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Cells, Cultured
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DNA-Binding Proteins / drug effects
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DNA-Binding Proteins / metabolism*
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Feedback, Physiological / drug effects
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Feedback, Physiological / immunology
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Heme Oxygenase (Decyclizing) / drug effects
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Heme Oxygenase (Decyclizing) / immunology
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Heme Oxygenase (Decyclizing) / metabolism*
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Heme Oxygenase-1
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Humans
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Inflammation / chemically induced
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Inflammation / enzymology
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Inflammation / immunology
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Interleukin-10 / immunology
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Interleukin-10 / metabolism*
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Interleukin-10 / pharmacology
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Interleukin-6 / metabolism
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Interleukin-6 / pharmacology
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Lipopolysaccharides / pharmacology
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Macrophages / drug effects
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Macrophages / enzymology*
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Macrophages / immunology
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Male
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Membrane Proteins
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Mice
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Mice, Inbred BALB C
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Monocytes / drug effects
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Monocytes / enzymology
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Monocytes / immunology
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Phosphatidylinositol 3-Kinases / drug effects
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Phosphatidylinositol 3-Kinases / metabolism*
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Protoporphyrins / pharmacology
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STAT3 Transcription Factor
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Signal Transduction / drug effects
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Signal Transduction / immunology
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Trans-Activators / drug effects
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Trans-Activators / metabolism*
Substances
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Anti-Inflammatory Agents
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DNA-Binding Proteins
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Interleukin-6
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Lipopolysaccharides
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Membrane Proteins
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Protoporphyrins
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STAT3 Transcription Factor
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STAT3 protein, human
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Stat3 protein, mouse
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Trans-Activators
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Interleukin-10
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zinc protoporphyrin
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HMOX1 protein, human
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Heme Oxygenase (Decyclizing)
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Heme Oxygenase-1
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Hmox1 protein, mouse
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Phosphatidylinositol 3-Kinases