This Article Full Text Full Text (PDF) Supplemental Material Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hardman, M. J. Articles by Ashcroft, G. S. Search for Related Content PubMed PubMed Citation Articles by Hardman, M. J. Articles by Ashcroft, G. S.

(American Journal of Pathology. 2005;167:1561-1574.)
© 2005 American Society for Investigative Pathology

Macrophage Migration Inhibitory Factor

A Central Regulator of Wound Healing

Matthew J. Hardman^*, Alexander Waite^*, Leo Zeef^*, Matthew Burow, Toshinori Nakayama and Gillian S. Ashcroft^*

From the Faculty of Life Sciences,^* University of Manchester, Manchester, United Kingdom; the Tulane University School of Medicine, New Orleans, Louisiana; and the Department of Molecular Immunology, Chiba University Graduate School of Medicine, Chiba, Japan

Age-associated differences in estrogen levels critically modify the cutaneous wound healing response. Using a microarray-based approach, we profiled changes in gene expression within the wounds of mice that were wild type or null for the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) in the presence or absence of estrogen. This experimental design identified more than 600 differentially expressed genes and established MIF as a key player in the wound healing process, regulating many novel repair/inflammation-associated gene targets. Moreover, MIF affected virtually all of the effects of reduced estrogen on wound repair. In humans, serum and wound levels of MIF increased with age and were strongly down-regulated by estrogen in vivo. Estrogen-regulated MIF transcription in vitro via a nuclear factor B-dependent mechanism. These findings have wide-ranging implications for the many pathophysiological states in which MIF plays an important regulatory role and suggest a potential therapeutic role for MIF in modulating clinical conditions associated with age-related decline in estrogen levels.

This article has been cited by other articles:

				T. Matsumoto Can Active Immunization Against Macrophage Migration Inhibitory Factor by DNA Vaccination Prevent Postmenopausal Osteoporosis? IBMS BoneKEy, June 1, 2008; 5(6): 209 - 211. [Full Text] [PDF]

				M. Krockenberger, Y. Dombrowski, C. Weidler, M. Ossadnik, A. Honig, S. Hausler, H. Voigt, J. C. Becker, L. Leng, A. Steinle, et al. Macrophage Migration Inhibitory Factor Contributes to the Immune Escape of Ovarian Cancer by Down-Regulating NKG2D J. Immunol., June 1, 2008; 180(11): 7338 - 7348. [Abstract] [Full Text] [PDF]

				M. J. Hardman, E. Emmerson, L. Campbell, and G. S. Ashcroft Selective Estrogen Receptor Modulators Accelerate Cutaneous Wound Healing in Ovariectomized Female Mice Endocrinology, February 1, 2008; 149(2): 551 - 557. [Abstract] [Full Text] [PDF]

				Y.-C. Hsieh, M. Frink, C.-H. Hsieh, M. A. Choudhry, M. G. Schwacha, K. I. Bland, and I. H. Chaudry Downregulation of migration inhibitory factor is critical for estrogen-mediated attenuation of lung tissue damage following trauma-hemorrhage Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1227 - L1232. [Abstract] [Full Text] [PDF]

				A. Maity and C. Koumenis HIF and MIF--a nifty way to delay senescence? Genes & Dev., December 15, 2006; 20(24): 3337 - 3341. [Full Text] [PDF]