Сердечно-сосудистая фармакология: открытый доступ

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Thermo-Sensitive Transient Receptor Potential Vanilloid (TRPV) Channels Regulate IL-6 Expression in Mouse Adipocytes

Hironobu Kikuchi, Gaku Oguri, Yumiko Yamamoto, Nami Takano, Tomofumi Tanaka, Masao Takahashi, Fumitaka Nakamura, Tatsuya Yamasoba, Issei Komuro, Syotaro Obi, Toshiaki Nakajima

Background: Hyperthermia may affect adipose cell functions and then adipogenesis. Thermo-sensitive transient receptor potential (TRPs) proteins such as TRPV1-4 play vital roles in cellular functions. We investigated the expression of thermo-sensitive TRPVs and their roles on IL-6 production in mouse 3T3-L1 preadipocytes and differentiated adipocytes.

Methods: The conventional and quantitative real-time RT-PCR analysis, western blots, fluorescence activating cell sorting, immunocytochemical staining and [Ca2+]i measurements using fura-2 AM were performed.

Results: The conventional and real-time RT-PCR analysis showed the existence of TRPV1, 2 and 4 expressions. Western blotting and immunocytochemical staining also showed the existence of TRPV1, TRPV2 and TRPV4 transcript in 3T3-L1 preadipocytes and differentiated adipocytes. Capsaicin, a TRPV1 agonist, probenecid, a TRPV2 agonist, and GSK1016790A, a TRPV4 agonist, and 2-aminoethoxydiphenyl borate (2-APB), a TRPV1-3 selective agonist, increased [Ca2+]i. These changes were also elicited by a rise in extracellular temperature from 25°C to over 42°C. Treatment with capsaicin, GSK1016790A and probenecid for 24 h increased IL-6 expression, and secretion in differentiated adipocytes. Warm temperature from 25°C to over 42°C also induced IL-6 protein expression.

Conclusions: The present study shows that adipose cell possess multiple thermo-sensitive TRPVs (TRPV1, TRPV2, and TRPV4), which may play vital roles in IL-6 production. Thus, thermo-sensitive TRPVs appear to be novel target molecules for promoting IL-6 secretion in adipose tissues.