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

Title
Melanocortins induce interleukin 6 gene expression and secretion through melanocortin receptors 2 and 5 in 3T3-L1 adipocytes
Authors
Jun, DJNa, KYKim, WKwak, DKwon, EJYoon, JHYea, KLee, HKim, JSuh, PGRyu, SHKim, KT
POSTECH Authors
Kim, KT
Date Issued
Apr-2010
Publisher
BIOSCIENTIFICA LTD
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. alpha-Melanocyte-stimulating hormone (alpha-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 I kappa B kinase pathways. Specific inhibition of MC2R and MC5R expression with short interfering Mc2r and Mc5r RNAs significantly attenuated the alpha-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, alpha-MSH dramatically increased the Il6 transcript levels in epididymal fat pads. These results suggest that alpha-MSH in addition to ACTH may function as a regulator of inflammation by regulating cytokine production.
Keywords
NF-KAPPA-B; MELANOCYTE-STIMULATING HORMONE; NECROSIS-FACTOR-ALPHA; PROTEIN-KINASE-A; INSULIN-RESISTANCE; ADIPOSE-TISSUE; CYTOKINE PRODUCTION; IL-6 EXPRESSION; IN-VIVO; PATHWAY
URI
http://oasis.postech.ac.kr/handle/2014.oak/17449
DOI
10.1677/JME-09-0161
ISSN
0952-5041
Article Type
Article
Citation
JOURNAL OF MOLECULAR ENDOCRINOLOGY, vol. 44, no. 4, page. 225 - 236, 2010-04
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 KIM, KYONG TAI
Div of Integrative Biosci & Biotech
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