title: The effects of macrophage migratory inhibitory factor on acute-phase protein production in primary human hepatocytes.
abstract: Macrophage inhibitory factor (MIF) is a pituitary peptide released during the physiological stress response, a T-cell product secreted during the antigen-specific response and a pro-inflammatory macrophage cytokine secreted after LPS stimulation. It has become apparent that MIF is central to the regulation of the inflammatory response and is implicated in the pathogenesis of a variety of acute and chronic inflammatory conditions. This is, at least in part, due to the apparent counter-regulation of the anti-inflammatory actions of glucocorticoids, including the reversal of glucocorticoid-mediated IL-6 release inhibition. This study examines the effect of recombinant MIF on regulation of the acute phase response in isolated human hepatocytes. MIF alone increased C-reactive protein (CRP) release in a dose-dependent manner < or = 0.1 ng/ml after which the effects of MIF were attenuated. In combination with IL-6 both CRP and and alpha-1-antichymotrypsin (ACT) release were increased above levels found with either IL-6 or MIF treatment alone. Dexamethasone attenuated the effects of MIF upon CRP production but increased the MIF stimulated release of ACT. The study demonstrates that the effects of MIF upon the acute phase response are complex and can differentially modulate the production of acute phase proteins depending on the presence of other factors.
authors.affiliation: Tissue Injury & Repair Group, Centre for Regenerative Medicine, University of Edinburgh, The Chancellor's Building, Edinburgh EH16 4SB, UK.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Wheelhouse
authors.forename: Nabil
authors.initials: N
authors.lastname: Dowidar
authors.forename: Cornelis H C
authors.initials: CH
authors.lastname: Dejong
authors.forename: O James
authors.initials: OJ
authors.lastname: Garden
authors.forename: James J
authors.initials: JJ
authors.lastname: Powell
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Barber
authors.forename: Kathryn
authors.initials: K
authors.lastname: Sangster
authors.forename: Jean P
authors.initials: JP
authors.lastname: Maingay
authors.forename: James A
authors.initials: JA
authors.lastname: Ross
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D006505:Hepatitis / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; D011994:Recombinant Proteins; D000514:alpha 1-Antichymotrypsin; D003907:Dexamethasone; D002097:C-Reactive Protein