Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF-2 in adipose tissue during endotoxemia.

Kim BS; Tilstam PV; Arnke K; Leng L; Ruhl T; Piecychna M; Schulte W; Sauler M; Frueh FS; Storti G; Lindenblatt N; Giovanoli P; Pallua N; Bernhagen J; Bucala R

doi:10.1096/fj.201901511R

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Journal article

Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF-2 in adipose tissue during endotoxemia.

Kim BS Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
Tilstam PV Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
Arnke K Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland.
Leng L Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
Ruhl T Department of Plastic, Reconstructive and Hand Surgery, RWTH Aachen University, Aachen, Germany.
Piecychna M Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
Schulte W Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
Sauler M Department of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven, CT.
Frueh FS Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland.
Storti G Unit of Plastic and Reconstructive Surgery, University of Rome- "Tor Vergata", Rome, Italy.
Lindenblatt N Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland.
Giovanoli P Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland.
Pallua N Department of Plastic, Reconstructive and Hand Surgery, RWTH Aachen University, Aachen, Germany.
Bernhagen J Department of Vascular Biology, Institute for Stroke and Dementia Research, Ludwig-Maximilians-University Munich, Munich, Germany.
Bucala R Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.

2020-01-22

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FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - 2020

English Sepsis is a leading cause of death worldwide and recent studies have shown white adipose tissue (WAT) to be an important regulator in septic conditions. In the present study, the role of the inflammatory cytokine macrophage migration inhibitory factor (MIF) and its structural homolog D-dopachrome tautomerase (D-DT/MIF-2) were investigated in WAT in a murine endotoxemia model. Both MIF and MIF-2 levels were increased in the peritoneal fluid of LPS-challenged wild-type mice, yet, in visceral WAT, the proteins were differentially regulated, with elevated MIF but downregulated MIF-2 expression in adipocytes. Mif gene deletion polarized adipose tissue macrophages (ATM) toward an anti-inflammatory phenotype while Mif-2 gene knockout drove ATMs toward a pro-inflammatory phenotype and Mif-deficiency was found to increase fibroblast viability. Additionally, we observed the same differential regulation of these two MIF family proteins in human adipose tissue in septic vs healthy patients. Taken together, these data suggest an inverse relationship between adipocyte MIF and MIF-2 expression during systemic inflammation, with the downregulation of MIF-2 in fat tissue potentially increasing pro-inflammatory macrophage polarization to further drive adipose inflammation.

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