title: Macrophage migration inhibitory factor counter-regulates dexamethasone-induced annexin 1 expression and influences the release of eicosanoids in murine macrophages.
abstract: Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine and glucocorticoid (GC) counter-regulator, has emerged as an important modulator of inflammatory responses. However, the molecular mechanisms of MIF counter-regulation of GC still remain incomplete. In the present study, we investigated whether MIF mediated the counter-regulation of the anti-inflammatory effect of GC by affecting annexin 1 in RAW 264.7 macrophages. We found that stimulation of RAW 264.7 macrophages with lipopolysaccharide (LPS) resulted in down-regulation of annexin 1, while GC dexamethasone (Dex) or Dex plus LPS led to significant up-regulation of annexin 1 expression. RNA interference-mediated knockdown of intracellular MIF increased annexin 1 expression with or without incubation of Dex, whereas Dex-induced annexin 1 expression was counter-regulated by the exogenous application of recombinant MIF. Moreover, recombinant MIF counter-regulated, in a dose-dependent manner, inhibition of cytosolic phospholipase A2α (cPLA2α) activation and prostaglandin E2 (PGE2 ) and leukotriene B4 (LTB4 ) release by Dex in RAW 264.7 macrophages stimulated with LPS. Endogenous depletion of MIF enhanced the effects of Dex, reflected by further decease of cPLA2α expression and lower PGE2 and LTB4 release in RAW 264.7 macrophages. Based on these data, we suggest that MIF counter-regulates Dex-induced annexin 1 expression, further influencing the activation of cPLA2α and the release of eicosanoids. These findings will add new insights into the mechanisms of MIF counter-regulation of GC.
authors.affiliation: Burns Institute of Chinese PLA and Department of Burn Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Li
authors.forename: Shi-Hui
authors.initials: SH
authors.lastname: Zhu
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Tang
authors.forename: Zhao-Fan
authors.initials: ZF
authors.lastname: Xia
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000096:biosynthesis*; D015153:Blotting, Western; D003907:Dexamethasone / Q000494:pharmacology*; D015777:Eicosanoids / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D019746:Intramolecular Oxidoreductases / Q000276:immunology / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D017305:Annexin A1; D015777:Eicosanoids; D005938:Glucocorticoids; D008263:Macrophage Migration-Inhibitory Factors; D034741:RNA, Small Interfering; D003907:Dexamethasone; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse
keywords: annexin 1; glucocorticoids; leukotriene B4; macrophage migration inhibitory factor; prostaglandin E2