Endothelin-1 stimulates interleukin-6 secretion from 3T3-L1 adipocytes.
BACKGROUND
Since both endothelin-1 (ET-1) and interleukin-6 (IL-6) may induce insulin resistance and adipose tissue is a major contributor of circulating IL-6, we examined the effects of ET-1 on IL-6 secretion from 3T3-L1 adipocytes.


METHODS
IL-6 release was measured by ELISA. RT-PCR and real-time PCR analyses were used to determine cellular IL-6 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
Treatment of adipocytes with ET-1 dose- and time-dependently increased IL-6 secretion. The stimulatory effect of ET-1 on IL-6 secretion was abolished by actinomycin D and ET-1 induced an increase in IL-6 mRNA levels. ET-1 was able to enhance the IL-6 promoter activity and its stimulatory effect was inhibited by GF109203X, U0126, salicylate, dominant negative CREB and mithramycin A. Thus it appears that ET-1 may stimulate IL-6 secretion mainly through an enhanced IL-6 transcription, by a mechanism involving both protein kinase C and p42/p44 mitogen-activated protein kinase, and probably downstream NF-kappaB, CREB and Sp1 transcription factors.


CONCLUSIONS
This study demonstrates that ET-1 is able to increase IL-6 secretion from adipocytes and raises the possibility that ET-1-induced insulin resistance may be mediated by IL-6.
Chai
Shin-Pei
SP
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
Chang
Yin-Nan
YN
Fong
Jim C
JC
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003609:Dactinomycin / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects
D017931:DNA Primers; D019332:Endothelin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D003609:Dactinomycin