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Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF‐2 in adipose tissue during endotoxemia
Author(s) -
Kim BongSung,
Tilstam Pathricia V.,
Arnke Kevin,
Leng Lin,
Ruhl Tim,
Piecychna Marta,
Schulte Wibke,
Sauler Maor,
Frueh Florian S.,
Storti Gabriele,
Lindenblatt Nicole,
Giovanoli Pietro,
Pallua Norbert,
Bernhagen Jürgen,
Bucala Richard
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901511r
Subject(s) - macrophage migration inhibitory factor , adipose tissue , inflammation , cytokine , adipose tissue macrophages , fgf21 , adipocyte , macrophage polarization , endocrinology , white adipose tissue , biology , downregulation and upregulation , medicine , macrophage , immunology , fibroblast growth factor , receptor , gene , biochemistry , in vitro
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.