Premium
Heme oxygenase 1 expression induced by IL‐10 requires STAT‐3 and phosphoinositol‐3 kinase and is inhibited by lipopolysaccharide
Author(s) -
Ricchetti Giuseppe A.,
Williams Lynn M.,
Foxwell Brian M. J.
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0104046
Subject(s) - heme oxygenase , biology , stat protein , cytokine , microbiology and biotechnology , p38 mitogen activated protein kinases , stat , signal transduction , protein kinase a , kinase , heme , stat3 , immunology , biochemistry , enzyme
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.