Cross-talk between α1B-Adrenergic Receptor (α1BAR) and Interleukin-6 (IL-6) Signaling Pathways

Treatment of primary rat hepatocytes or tranfected HepG2 cells with the α 1B -adrenergic receptor (α 1B AR) agonist phenylephrine (PE) significantly inhibited interleukin 6 (IL-6)-induced STAT3 binding, tyrosine phosphorylation, and IL-6-induced serum amyloid A mRNA expression. Western analyses an...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-12, Vol.274 (50), p.35492
Main Authors: Van-Anh T. Nguyen, Bin Gao
Format: Article
Language:English
Online Access:Get full text
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Summary:Treatment of primary rat hepatocytes or tranfected HepG2 cells with the α 1B -adrenergic receptor (α 1B AR) agonist phenylephrine (PE) significantly inhibited interleukin 6 (IL-6)-induced STAT3 binding, tyrosine phosphorylation, and IL-6-induced serum amyloid A mRNA expression. Western analyses and in vitro kinase assays indicate that this inhibition is not due to either down-regulation of STAT3 protein expression nor inactivation of upstream-located JAK1 and JAK2. Blocking the new RNA and protein syntheses antagonized the inhibitory effect of PE on IL-6-activated STAT3, suggesting synthesis of an inhibitory factor(s) is involved. The inhibitory effect of PE on IL-6 activation of STAT3 was also abolished by the tyrosine phosphatase inhibitor sodium vanadate, indicating involvement of protein tyrosine phosphatases. Furthermore, preincubation of the cells with the specific MEK1 inhibitor PD98059 or a dominant negative MEK1 reversed the inhibitory effect of PE, and expression of constitutively activated MEK1 alone abolished IL-6-activated STAT3. Taken together, these data indicate that PE inhibits IL-6 activation of STAT3 in hepatic cells by a p42/44 mitogen-activated protein kinase-dependent mechanism, and tyrosine phosphatases are involved. This inhibitory cross-talk between the α 1B AR and IL-6 signaling pathways implicates the α 1B AR involvement in regulating the IL-6-mediated inflammatory responses.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.274.50.35492