Nature medicine, 2002-03, Vol.8 (3), p.240-246
2002
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice
- Ist Teil von
- Nature medicine, 2002-03, Vol.8 (3), p.240-246
- Ort / Verlag
- United States: Nature Publishing Group
- Erscheinungsjahr
- 2002
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The mechanisms underlying the action of the potent anti-inflammatory interleukin-10 (IL-10) are poorly understood. Here we show that, in murine macrophages, IL-10 induces expression of heme oxygenase-1 (HO-1), a stress-inducible protein with potential anti-inflammatory effect, via a p38 mitogen-activated protein kinase-dependent pathway. Inhibition of HO-1 protein synthesis or activity significantly reversed the inhibitory effect of IL-10 on production of tumor necrosis factor-alpha induced by lipopolysaccharide (LPS). Additional experiments revealed the involvement of carbon monoxide, one of the products of HO-1-mediated heme degradation, in the anti-inflammatory effect of IL-10 in vitro. Induction of HO-1 by IL-10 was also evident in vivo. IL-10-mediated protection against LPS-induced septic shock in mice was significantly attenuated by cotreatment with the HO inhibitor, zinc protoporphyrin. The identification of HO-1 as a downstream effector of IL-10 provides new possibilities for improved therapeutic approaches for treating inflammatory diseases.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1078-8956eISSN: 1546-170XDOI: 10.1038/nm0302-240Titel-ID: cdi_proquest_miscellaneous_71530365
- Format
- –
- Schlagworte
- Animals, Anti-Inflammatory Agents - metabolism, Carbon monoxide, Cells, Cultured, Cytokines, Enzyme Activation, Enzyme Induction, Enzyme Inhibitors - pharmacology, Gene expression, Heme Oxygenase (Decyclizing) - antagonists & inhibitors, Heme Oxygenase (Decyclizing) - genetics, Heme Oxygenase (Decyclizing) - metabolism, Heme Oxygenase-1, Humans, Interleukin-10 - pharmacology, Interleukin-10 - physiology, Interleukin-6 - pharmacology, Kinases, Lipopolysaccharides - pharmacology, Macrophages, Peritoneal - drug effects, Macrophages, Peritoneal - physiology, Male, Matrix Metalloproteinase 9 - metabolism, Membrane Proteins, Mice, Mice, Inbred BALB C, Mitogen-Activated Protein Kinases - antagonists & inhibitors, Mitogen-Activated Protein Kinases - metabolism, Nitric Oxide Synthase - genetics, Nitric Oxide Synthase - metabolism, Nitric Oxide Synthase Type II, Oligodeoxyribonucleotides, Antisense - metabolism, p38 Mitogen-Activated Protein Kinases, Phosphorylation, Protein synthesis, Proteins, Proteins - metabolism, Protoporphyrins - pharmacology, Repressor Proteins, Sepsis, Signal Transduction, stress-inducible proteins, Suppressor of Cytokine Signaling 3 Protein, Suppressor of Cytokine Signaling Proteins, Transcription Factors, Tumor Necrosis Factor-alpha - metabolism, Tumor necrosis factor-TNF