Macrophage migration inhibitory factor antagonizes hydrocortisone-induced increases in cytosolic IkBa

Daun, Jane M., and Joseph G. Cannon. Macrophage migration inhibitory factor antagonizes hydrocortisone-induced increases in cytosolic IkBa. Am J Physiol Regulatory Integrative Comp Physiol 279: R1043–R1049, 2000.—Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine secreted by several cell types, including mononuclear and pituitary cells. It has also been shown to counteract cortisol-induced inhibition of inflammatory cytokine secretion. The purpose of this study was to determine whether MIF antagonized the effect of hydrocortisone on the NF-kB/IkB signal transduction pathway in lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells. Physiological doses of hydrocortisone (50–200 ng/ml) diminished both the LPS-stimulated decrease in cytosolic IkBa levels and the subsequent increase in nuclear NF-kB DNA binding. In the presence of both LPS and hydrocortisone, 1 ng/ml of MIF antagonized the effects of hydrocortisone, resulting in decreased cytosolic IkBa levels (P , 0.05) and increased nuclear NF-kB DNA binding (P , 0.05). In the absence of hydrocortisone, MIF had no effect on LPSinduced decreases in IkBa. In the absence of LPS, MIF inhibited hydrocortisone-induced increases in IkBa (P 5 0.03). Thus the mechanism by which MIF antagonizes the effect of hydrocortisone on the NF-kB/IkB signal transduction pathway is through inhibiting the ability of hydrocortisone to increase cytosolic IkBa.