Melanocortins induce interleukin 6 gene expression and secretion through melanocortin receptors 2 and 5 in 3T3-L1 adipocytes

Dong Jae Jun, Kyung Yoon Na, Wanil Kim, Dongoh Kwak, Eun Jeong Kwon, Jong Hyuk Yoon, Kyungmoo Yea, Hyeongji Lee, Jaeyoon Kim, Pann Gill Suh, Sung Ho Ryu, Kyong Tai Kim

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Interleukin 6 (IL6) is a pleiotropic cytokine that not only affects the immune system, but also plays an active role in many physiological events in various organs. Notably, 35% of systemic IL6 originates from adipose tissues under noninflammatory conditions. Here, we describe a previously unknown function of melanocortins in regulating Il6 gene expression and production in 3T3-L1 adipocytes through membrane receptors which are called melanocortin receptors (MCRs). Of the five MCRs that have been cloned, MC2R and MC5R are expressed during adipocyte differentiation. α-Melanocyte-stimulating hormone (α-MSH) or ACTH treatment of 3T3-L1 adipocytes induces Il6 gene expression and production in a time- and concentration-dependent manner via various signaling pathways including the protein kinase A, p38 mitogen-activated protein kinase, cJun N-terminal kinase, and IκB kinase pathways. Specific inhibition of MC2R and MC5R expression with short interfering Mc2r and Mc5r RNAs significantly attenuated the α-MSH-induced increase of intracellular cAMP and both the level of Il6 mRNA and secretion of IL6 in 3T3-L1 adipocytes. Finally, when injected into mouse tail vein, α-MSH dramatically increased the Il6 transcript levels in epididymal fat pads. These results suggest that α-MSH in addition to ACTH may function as a regulator of inflammation by regulating cytokine production.

Original languageEnglish
Pages (from-to)225-236
Number of pages12
JournalJournal of Molecular Endocrinology
Volume44
Issue number4
DOIs
StatePublished - Apr 2010

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