Macrophage migration inhibitory factor (MIF) promotes fibroblast migration in scratch-wounded monolayers in vitro

Dewor, Manfred; Steffens, Guy; Krohn, Regina; Weber, Christian; Baron, Jens; Bernhagen, Jürgen

doi:10.1016/j.febslet.2007.08.071

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Volume 581, Issue 24 , Pages 4734-4742, 2 October 2007

Macrophage migration inhibitory factor (MIF) promotes fibroblast migration in scratch-wounded monolayers in vitro

Edited by Beat Imhof

Manfred Dewor
- Department of Biochemistry and Molecular Cell Biology, Institute of Biochemistry, University Hospital RWTH Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany
- These authors contributed equally to this work.
Guy Steffens
- Department of Biochemistry and Molecular Cell Biology, Institute of Biochemistry, University Hospital RWTH Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany
- These authors contributed equally to this work.
Regina Krohn
- Institute of Molecular and Cardiovascular Research, University Hospital RWTH Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany
Christian Weber
- Institute of Molecular and Cardiovascular Research, University Hospital RWTH Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany
Jens Baron
- Department of Dermatology and Allergology, University Hospital RWTH Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany
Jürgen Bernhagen
- Department of Biochemistry and Molecular Cell Biology, Institute of Biochemistry, University Hospital RWTH Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany
- Corresponding author.

Received 25 June 2007; received in revised form 13 August 2007; accepted 29 August 2007. published online 06 September 2007.

Abstract

MIF was recently redefined as an inflammatory cytokine, which functions as a critical mediator of diseases such as septic shock, rheumatoid arthritis, atherosclerosis, and cancer. MIF also regulates wound healing processes. Given that fibroblast migration is a central event in wound healing and that MIF was recently demonstrated to promote leukocyte migration through an interaction with G-protein-coupled receptors, we investigated the effect of MIF on fibroblast migration in wounded monolayers in vitro. Transient but not permanent exposure of primary mouse or human fibroblasts with MIF significantly promoted wound closure, a response that encompassed both a proliferative and a pro-migratory component. Importantly, MIF-induced fibroblast activation was accompanied by an induction of calcium signalling, whereas chronic exposure with MIF down-regulated the calcium transient, suggesting receptor desensitization as the underlying mechanism.

Abbreviations: CXCR, CXC chemokine receptor, GPCR, G-protein-coupled receptor, HFDFs, human foreskin dermal fibroblasts, MEFs, mouse embryonic fibroblasts, MIF, macrophage migration inhibitory factor, rMIF, recombinant human MIF, wt, wild-type, wtMEFs, wild-type MEFs