Melanocortins induce interleukin 6 gene expression and secretion through melanocortin receptors 2 and 5 in 3T3-L1 adipocytes.
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.
Jun
Dong-Jae
DJ
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.
Na
Kyung-Yoon
KY
Kim
Wanil
W
Kwak
Dongoh
D
Kwon
Eun-Jeong
EJ
Yoon
Jong Hyuk
JH
Yea
Kyungmoo
K
Lee
Hyeongji
H
Kim
Jaeyoon
J
Suh
Pann-Gill
PG
Ryu
Sung Ho
SH
Kim
Kyong-Tai
KT
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
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