Macrophage migration inhibitory factor (MIF) promotes fibroblast migration in scratch-wounded monolayers in vitro.
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.
Dewor
Manfred
M
Department of Biochemistry and Molecular Cell Biology, Institute of Biochemistry, University Hospital RWTH Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany.
Steffens
Guy
G
Krohn
Regina
R
Weber
Christian
C
Baron
Jens
J
Bernhagen
Jürgen
J
D000818:Animals; D020013:Calcium Signaling; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D013997:Time Factors; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology*
D008263:Macrophage Migration-Inhibitory Factors