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.

Kim, B.-., Tilstam, P.v., Arnke, K., Leng, L., Ruhl, T., Piecychna, M., et al. (2020). Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF-2 in adipose tissue during endotoxemia. FASEB JOURNAL, 34(3), 4219-4233 [10.1096/fj.201901511R].

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

Storti G.;
2020-01-01

Abstract

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.
2020
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/19 - CHIRURGIA PLASTICA
English
D-DT
MIF
MIF-2
adipose tissue
inflammation
macrophage
macrophage polarization
sepsis
wound healing
3T3 Cells
Adipocytes
Adipose Tissue
Adipose Tissue, White
Animals
Cells, Cultured
Endotoxemia
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Intramolecular Oxidoreductases
Macrophage Activation
Macrophage Migration-Inhibitory Factors
Macrophages, Peritoneal
Male
Mice
Mice, Inbred C57BL
Kim, B.-., Tilstam, P.v., Arnke, K., Leng, L., Ruhl, T., Piecychna, M., et al. (2020). Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF-2 in adipose tissue during endotoxemia. FASEB JOURNAL, 34(3), 4219-4233 [10.1096/fj.201901511R].
Kim, B-; Tilstam, Pv; Arnke, K; Leng, L; Ruhl, T; Piecychna, M; Schulte, W; Sauler, M; Frueh, Fs; Storti, G; Lindenblatt, N; Giovanoli, P; Pallua, N; ...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/296837
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