Abstract
Adipocytes interact with adipose tissue macrophages (ATMs) that exist as a form of M2 macrophage in healthy adipose tissue and are polarized into M1 macrophages upon cellular stress. ATMs regulate adipose tissue inflammation by secreting cytokines, adipokines, and chemokines. CXC-motif receptor 6 (CXCR6) is the chemokine receptor and interactions with its specific ligand CXC-motif chemokine ligand 16 (CXCL16) modulate the migratory capacities of human adipose-derived mesenchymal stem cells (hADMSCs). CXCR6 is highly expressed on differentiated adipocytes that are non-migratory cells. To evaluate the underlying mechanisms of CXCR6 in adipocytes, THP-1 human monocytes that can be polarized into M1 or M2 macrophages were co-cultured with adipocytes. As results, expression levels of the M1 polarization-inducing factor were decreased, while those of the M2 polarization-inducing factor were significantly increased in differentiated adipocytes in a co-cultured environment with additional CXCL16 treatment. After CXCL16 treatment, the anti-inflammatory factors, including p38 MAPK ad ERK1/2, were upregulated, while the pro-inflammatory pathway mediated by Akt and NF-κB was downregulated in adipocytes in a co-cultured environment. These results revealed that the CXCL16/CXCR6 axis in adipocytes regulates M1 or M2 polarization and displays an immunosuppressive effect by modulating pro-inflammatory or anti-inflammatory pathways. Our results may provide an insight into a potential target as a regulator of the immune response via the CXCL16/CXCR6 axis in adipocytes.
Highlights
Adipose tissue, which is generally recognized as a complex metabolic organ, produces various factors which have important endocrine functions, including cytokines, chemokines, and adipokines, such as leptin and adiponectin [1,2]
The secretion levels of tumor necrosis factor-α (TNF-α) and IL-10 in a co-cultured media of differentiated adipocytes and THP-1 cells were significantly decreased and increased, respectively, consistent with the data shown in Figure 3B,C (Figure 4C,D). These results suggest that CXCmotif chemokine ligand 16 (CXCL16) interacts with CXC-motif receptor 6 (CXCR6), which is highly expressed in differentiated adipocytes, and regulates the polarization of THP-1 cells into M1 or M2 macrophages via the secretion of factors including TNF-α and IL-10
We investigated the role of CXCR6 in differentiated adipocytes in interaction with macrophages after CXCL16 treatment
Summary
Adipose tissue, which is generally recognized as a complex metabolic organ, produces various factors which have important endocrine functions, including cytokines, chemokines, and adipokines, such as leptin and adiponectin [1,2]. Of these factors, circulating inflammatory chemokines are strongly associated with obesity, which is a state of chronic low-grade systemic inflammation, and the development of allergic or immune diseases as a result of their interaction with macrophages [3,4]. Alternatively activated M2 macrophages are distributed in healthy adipose tissue via the expression of anti-inflammatory factors, such as fibronectin, cluster of differentiation 206 (CD 206), C–C motif chemokine ligand 22
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