Chemokine network during adipogenesis in 3T3-L1 cells: Differential response between growth and proinflammatory factor in preadipocytes vs. adipocytes.
Obesity is recognized as a low-grade chronic inflammatory state which involves a chemokine network contributing to a variety of diseases. As a first step toward understanding the roles of the obesity-driven chemokine network, we used a 3T3-L1 cell differentiation model to identify the chemokine profiles elicited during adipogenesis and how this profile is modified by epidermal growth factor (EGF) and tumor necrosis factor-α (TNF) as a growth and proinflammatory factor, respectively. The chemokine network was monitored using PCR arrays and qRT-PCR while main signaling pathways of EGF and TNF were measured using immunoblotting. The dominant chemokines in preadipocytes were CCL5, CCL8, CXCL1, and CXCL16, and in adipocytes CCL6 and CXCL13. The following chemokines were found in both preadipocytes and adipocytes: CCL2, CCL7, CCL25, CCL27, CXCL5, CXCL12, and CX3CL1. Among chemokine receptors, CXCR7 was specific for preadipocytes and CXCR2 for adipocytes. These findings indicate the development of a CXCL12-CXCR7 axis in preadipocytes and a CXCL5-CXCR2 axis in adipocytes. In addition to induction of CCL2 and CCL7 in both preadipocytes and adipocytes, EGF enhanced specifically CXCL1 and CXCL5 in adipocytes, indicating the potentiation of CXCR2-mediated pathway in adipocytes. TNF induced CCL2, CCL7, and CXCL1 in preadipocytes but had no response in adipocytes. EGFR downstream activation was dominant in adipocytes whereas NFκB activation was dominant in preadipocytes. Taken together, the adipocyte-driven chemokine network in the 3T3-L1 cell differentiation model involves CXCR2-mediated signaling which appears more potentiated to growth factors like EGF than proinflammatory factors like TNF.
Department of Biochemistry and Cancer Biology; Meharry Medical College; Nashville, TN USA.
Syeda M
SM
Kabir
Department of Physiology; Meharry Medical College; Nashville, TN USA.
Eun-Sook
ES
Lee
Department of Biochemistry and Cancer Biology; Meharry Medical College; Nashville, TN USA.
Deok-Soo
DS
Son
EGF; TNF; adipocytes; chemokines; obesity; preadipocytes