Synergistic induction of interleukin-6 expression by endothelin-1 and cyclic AMP in adipocytes

• Published in: International Journal of Obesity Vol. 37; no. 2; pp. 197 - 203
• Main Authors: Chai, S-P, Juan, C-C, Kao, P-H, Wang, D-H, Fong, J C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-02-2013; Nature Publishing Group
• Subjects: 3T3-L1 Cells; 631/208/199; 631/250/127/1213; 631/443/319/1642/393; Adenosine; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Animals; Biochemistry; Biological and medical sciences; Body fat; Catecholamines; Catecholamines - metabolism; Cells, Cultured; Cyclic adenylic acid; Cyclic AMP - metabolism; Cytokines; Endothelin-1 - metabolism; Enzyme-Linked Immunosorbent Assay; Enzymes; Epidemiology; Fat cells; Gene expression; Gene Expression Regulation; Genetic aspects; Health Promotion and Disease Prevention; Injection; Insulin resistance; Interleukin-6; Interleukin-6 - metabolism; Internal Medicine; Luciferases - metabolism; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; Mice, Inbred C57BL; Molecular biology; Norepinephrine - pharmacology; Obesity; original-article; Penicillin; Physiological aspects; Public Health; Real-Time Polymerase Chain Reaction; RNA, Messenger - metabolism; Tumor necrosis factor-TNF; Taiwan; United States > US; catecholamine; endothelin-1; cAMP; interleukin-6; adipocyte; Adipocyte; Obesity; Nutrition; Induction; Cytokine; Nutrition disorder; Cyclic AMP; Metabolic diseases; Endothelin 1; Catecholamine; Gene expression; Synergism; Interleukin 6; Interleukin 1; Nutritional status
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2012.11

BACKGROUND:
We have demonstrated previously that endothelin-1 (ET-1) may stimulate interleukin-6 (IL-6) release from 3T3-L1 adipocytes. In this study, we further examined the combined effect of ET-1 and cyclic adenosine monophosphate (cAMP) on IL-6 release.
METHODS:
IL-6 release was measured by enzyme-linked immuosorbent assay. Reverse transcriptase-PCR and real-time PCR analyses were used to determine cellular mRNA levels. A luciferase reporter driven by promoter (−1310/+198) of mouse IL-6 gene was transfected into 3T3-L1 adipocytes to monitor IL-6 transcription.
RESULTS:
ET-1 and cAMP induced IL-6 release in a synergistic manner that can be attributed to their synergistic induction of IL-6 gene expression, as evidenced by IL-6 mRNA analysis and the IL-6 promoter reporter assay. Both ET
A
and ET
B
receptors seem to be involved. In addition, enhanced IL-6 promoter activity can be similarly induced by ET-1 and catecholamines (epinephrine and norepinephrine). The cooperative interaction between ET-1 and cAMP on IL-6 expression seems distinctive, as no other proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and IL-1β, are similarly affected. In fact, cAMP inhibited ET-1-stimulated TNF-α and IL-1β expressions in adipocytes. Furthermore, injection of mice with epinephrine and ET-1 induced a tremendously synergistic increase in serum IL-6 levels. Nevertheless, whereas cAMP induced IL-6 expression in RAW264.7 mouse macrophages, ET-1 had no effect on either the basal or the cAMP-induced IL-6 expression.
CONCLUSION:
ET-1 and epinephrine may boost plasma IL-6 levels in mice in a synergistic manner, probably through their synergistic induction of IL-6 expression in adipocytes.
SIGNIFICANCE:
This study should provide a new perspective for treating IL-6-related diseases, especially those accompanied with elevated ET-1 and catecholamine levels.