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Endogenous macrophage migration inhibitory factor modulates glucocorticoid sensitivity in macrophages via effects on MAP kinase phosphatase‐1 and p38 MAP kinase
Author(s) -
Aeberli Daniel,
Yang Yuan,
Mansell Ashley,
Santos Lanie,
Leech Michelle,
Morand Eric F.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.01.027
Subject(s) - macrophage migration inhibitory factor , p38 mitogen activated protein kinases , mitogen activated protein kinase , mapk/erk pathway , kinase , phosphorylation , phosphatase , endogeny , glucocorticoid , protein kinase a , microbiology and biotechnology , cytokine , chemistry , biology , endocrinology , immunology
The pro‐inflammatory cytokine macrophage migration inhibitory factor (MIF) is induced by glucocorticoids (GCs), but it was not previously known if MIF regulates cellular sensitivity to GC. Here we show in GC and LPS‐treated peritoneal macrophages derived from MIF−/− and wt mice that the absence of endogenous MIF is associated with increased sensitivity to GC of TNF release. This is associated with increased expression of mitogen‐activated protein kinase (MAPK) phosphatase‐1 (MKP‐1), concomitant decreased phosphorylation of p38 MAPK, but no effect of MIF on nuclear factor κB (NF‐κB). These results demonstrate that MIF regulates GC sensitivity by phosphorylation of p38, and provides a cellular mechanism for this observation, indicating that MKP‐1 is a central target of this regulation.