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Stimulation of transient receptor potential M3 (TRPM3) channels increases interleukin-8 gene promoter activity involving AP-1 and extracellular signal-regulated protein kinase.

Abstract：

:Stimulation of Ca2+ permeable TRPM3 (transient receptor potential melastatin-3) channels with the steroid ligand pregnenolone sulfate activates stimulus-responsive transcription factors, including the transcription factor AP-1 (activator protein-1). As part of a search for AP-1-regulated target genes we analyzed the gene encoding interleukin-8 (IL-8) in HEK293 cells expressing TRPM3 channels. Here, we show that stimulation of TRPM3 channels activated transcription of an IL-8 promoter-controlled reporter gene that was embedded into the chromatin of the cells. Mutational analysis of the IL-8 promoter revealed that the AP-1 binding site of the IL-8 promoter was essential to connect TRPM3 stimulation with the transcription of the IL-8 gene. Genetic experiments revealed that the basic region leucine zipper proteins c-Jun and ATF2 and the ternary complex factor Elk-1 are essential to couple TRPM3 channel stimulation with the IL-8 gene. Moreover, we identified extracellular signal-regulated protein kinase (ERK1/2) as signal transducer connecting TRPM3 stimulation with enhanced transcription of the IL-8 gene. Furthermore, we show that stimulation of TRPC6 (transient receptor potential canonical-6) channels with its ligand hyperforin also increased IL-8 promoter activity, involving the AP-1 binding site within the IL-8 gene, suggesting that activation of IL-8 gene transcription may be a common theme following TRP channel stimulation.

journal_name

Cytokine

journal_title

Cytokine

authors

Rubil S,Lesch A,Mukaida N,Thiel G

doi

10.1016/j.cyto.2017.09.020

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

133-141

eissn

1043-4666

issn

1096-0023

pii

S1043-4666(17)30277-6

journal_volume

103

pub_type

杂志文章

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