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

Jane M. Daun, Joseph G. Cannon

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

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 secrauton. The purpose of this study was to determine whether MIF antagonized the effect of hydrocortisone on the NF-κB/IκB 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 IκBα levels and the subsequent increase in nuclear NF-κB DNA binding. In the presence of both LPS and hydrocortisone, 1 ng/ml of MIF antagonized the effects of hydrocortisone, resulting in decreased cytosolic IκBα levels (P < 0.05) and increased nuclear NF-κB DNA binding (P < 0.05). In the absence of hydrocortisone, MIF had no effect on LPS-induced decreases in IκBα. In the absence of LPS, MIF inhibited hydrocortisone-induced increases in IκBα (P = 0.03). Thus the mechanism by which MIF antagonizes the effect of hydrocortisone on the NF-kB/IκB signal transduction pathway is through inhibiting the ability of hydrocortisone to increase cytosolic IκBα.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume279
Issue number3 48-3
StatePublished - Oct 3 2000

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Macrophage Migration-Inhibitory Factors
Hydrocortisone
Lipopolysaccharides
Signal Transduction
Cytokines
NF-kappa B
DNA
Blood Cells

Keywords

  • Glucocorticoids
  • Monocytes
  • NF-κB

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Macrophage migration inhibitory factor antagonizes hydrocortisone-induced increases in cytosolic IκBα. / Daun, Jane M.; Cannon, Joseph G.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 279, No. 3 48-3, 03.10.2000.

Research output: Contribution to journalArticle

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