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

International Journal of Obesity volume 37, pages 197–203 (2013)Cite this article

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Abstract

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 ETA and ETB 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.

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Acknowledgements

This study was supported by grants from Ministry of Education, Aim for the Top University Plan and National Science Council (NSC98-2320-B-010-019-MY3), ROC.

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Authors and Affiliations

  1. Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, ROC

    S-P Chai, P-H Kao, D-H Wang & J C Fong

  2. Institute of Physiology, National Yang-Ming University, Taipei, Taiwan, ROC

    C-C Juan

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Correspondence to J C Fong.

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Chai, SP., Juan, CC., Kao, PH. et al. Synergistic induction of interleukin-6 expression by endothelin-1 and cyclic AMP in adipocytes. Int J Obes 37, 197–203 (2013). https://doi.org/10.1038/ijo.2012.11

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