Macrophages inhibit adipogenic differentiation of adipose tissue derived mesenchymal stem/stromal cells by producing pro-inflammatory cytokines

Hui Ma; Ya-Nan Li; Lin Song; Rui Liu; Xiaolei Li; Qianwen Shang; Ying Wang; Changshun Shao; Yufang Shi

doi:10.1186/s13578-020-00450-y

Macrophages inhibit adipogenic differentiation of adipose tissue derived mesenchymal stem/stromal cells by producing pro-inflammatory cytokines

Cell Biosci. 2020 Jul 20:10:88. doi: 10.1186/s13578-020-00450-y. eCollection 2020.

Authors

Hui Ma^#¹, Ya-Nan Li^#¹, Lin Song¹, Rui Liu¹, Xiaolei Li¹, Qianwen Shang¹, Ying Wang², Changshun Shao³, Yufang Shi¹

Affiliations

¹ The First Affiliated Hospital of Soochow University, Institutes for Translational Medicine, State Key Laboratory of Radiation Medicine and Protection, Key Laboratory of Stem Cells and Medical Biomaterials of Jiangsu Province, Medical College of Soochow University, Suzhou, 215123 Jiangsu China.
² CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031 China.
³ Institutes for Translational Medicine, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123 Jiangsu China.

^# Contributed equally.

Abstract

Background: Mesenchymal stem/stromal cells (MSCs) and macrophages are critical components in many tissue microenvironments, including that in adipose tissue. The close interaction between MSCs and macrophages modulates various adipose-related disease development. However, the effects of macrophages on the fate of MSCs remain largely elusive. We here studied the effect of macrophages on the adipogenic differentiation of MSCs.

Methods: Macrophages were obtained from THP-1 cells treated with phorbol-12-myristate-13-acetate (PMA). The induced matured macrophages were then induced to undergo classically activated macrophage (M1) or alternatively activated macrophage (M2) polarization with Iipopolysaccharide (LPS)/interferon (IFN)-γ and interleukin (IL)-4/IL-13, respectively. The supernatants derived from macrophages under different conditions were applied to cultured human adipose tissue-derived mesenchymal stem/stromal cells (hADSCs) undergoing adipogenic differentiation. Adipogenic differentiation was evaluated by examining Oil Red O staining of lipid droplets and the expression of adipogenesis-related genes with real-time quantitative polymerase chain reaction (Q-PCR) and western blot analysis.

Results: The adipogenic differentiation of hADSCs was impaired when treated with macrophage-derived supernatants, especially that from the M1-polarized macrophage (M1-sup). The inhibitory effect was found to be mediated by the inflammatory cytokines, mainly tumor necrosis factor-α (TNF-α) and IL-1β. Blocking TNF-α and IL-1β with neutralizing antibodies partially alleviated the inhibitory effect of M1-sup.

Conclusion: Macrophage-derived supernatants inhibited the adipogenic differentiation of hADSCs in vitro, irrespective of the polarization status (M0, M1 or M2 macrophages). M1-sup was more potent because of the higher expression of pro-inflammatory cytokines. Our findings shed new light on the interaction between hADSCs and macrophages and have implications in our understanding of disrupted adipose tissue homeostasis under inflammation.

Keywords: Adipogenesis; Inflammation cytokines; Macrophages; hADSCs.