title: Melanocortins induce interleukin 6 gene expression and secretion through melanocortin receptors 2 and 5 in 3T3-L1 adipocytes.
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 IkappaB 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.
authors.affiliation: Division of Molecular and Life Science, Department of Life Science, Pohang University of Science and Technology (POSTECH), San 31, Hyoja Dong, Pohang 790-784, Republic of Korea.
authors.forename: Dong-Jae
authors.initials: DJ
authors.lastname: Jun
authors.forename: Kyung-Yoon
authors.initials: KY
authors.lastname: Na
authors.forename: Wanil
authors.initials: W
authors.lastname: Kim
authors.forename: Dongoh
authors.initials: D
authors.lastname: Kwak
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Kwon
authors.forename: Jong Hyuk
authors.initials: JH
authors.lastname: Yoon
authors.forename: Kyungmoo
authors.initials: K
authors.lastname: Yea
authors.forename: Hyeongji
authors.initials: H
authors.lastname: Lee
authors.forename: Jaeyoon
authors.initials: J
authors.lastname: Kim
authors.forename: Pann-Gill
authors.initials: PG
authors.lastname: Suh
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D041721:3T3-L1 Cells / Q000166:cytology / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D051550:I-kappa B Kinase / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D053486:Melanocortins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics / Q000378:metabolism*; D044101:Receptors, Melanocortin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000521:alpha-MSH / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D053486:Melanocortins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D044103:Receptor, Melanocortin, Type 2; D044101:Receptors, Melanocortin; C086971:melanocortin 5 receptor; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D051550:I-kappa B Kinase; D017868:Cyclic AMP-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases