Targetted inhibition of CD74 attenuates adipose COX-2-MIF-mediated M1 macrophage polarization and retards obesity-related adipose tissue inflammation and insulin resistance

Clinical Science
Pei-Chi ChanPo Shiuan Hsieh

Abstract

Adipose tissue (AT) inflammation is crucial to the development of obesity-associated insulin resistance. Our aim was to investigate the contribution of cyclooxygenase-2 (COX-2)/macrophage migration inhibitory factor (MIF)-mediated cross-talk between hypertrophic adipocytes and macrophages to the etiology of AT inflammation and the involvement of CD74 using human SGBS adipocytes, THP-1 macrophages and mice fed a high-fat (HF) diet. The MIF and CD74 mRNA levels in the adipocytes and stromal vascular cells (SVCs) of white fat were highly correlated with body weight (BW), homeostatic model assessment for insulin resistance (HOMA-IR), and adipose macrophage marker expression levels, especially those in SVCs. COX-2 inhibition suppressed the elevation of MIF production in HF white adipocytes as well as palmitate and hypoxic-treated SGBS adipocytes. Treatment of adipocytes transfected with shCOX-2 and siMIF or subjected to MIF depletion in the medium reversed the pro-inflammatory responses in co-incubated THP-1 cells. Inhibition of NF-κB activation reversed the COX2-dependent MIF secretion from treated adipocytes. The targetted inhibition of macrophage CD74 prevented M1 macrophage polarization in the above co-culture model. The COX-2-d...Continue Reading

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Citations

Dec 30, 2018·Scandinavian Journal of Immunology·Gholamreza DaryaborKurosh Kalantar
May 23, 2020·Bioengineering & Translational Medicine·Amrita Banerjee, Jagdish Singh
Jun 30, 2019·International Journal of Molecular Sciences·Pei-Chi ChanPo-Shiuan Hsieh
Nov 7, 2018·Journal of Neuroinflammation·V Alexandra MoserChristian J Pike
Aug 11, 2019·Cytokine·Stanislava Stošić-GrujičićIvana Stojanović
Jul 23, 2021·Frontiers in Endocrinology·Sara AndradeMariana P Monteiro

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