Cross-talk between bradykinin and epidermal growth factor in regulating IL-6 production in human airway smooth muscle cells

Po Hao Feng, Te Chih Hsiung, Han Pin Kuo, Chien Da Huang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Bradykinin (BK), a G-protein-coupled-receptor (GPCR) agonist via the B2 receptor induces interleukin (IL)-6 expression in airway smooth muscle (ASM) cells by involving the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. In some cell species, GPCR agonists have been shown to activate the ERK 1/2 pathway via transactivation of epidermal growth factor (EGF) receptor (EGFR). In this study, we tested whether there is cross-talk between BK and EGF in the regulation of IL-6 gene expression in ASM cells. Methods: ASM cells were treated with BK, EGF, AG-1478 and genistein. IL-6 production was analyzed by enzyme-linked immunosorbent assay (ELISA). Immunoblot study was used for detection of ERK1/2 activation. Transactivation of EGFR phosphorylation was detected by immunoprecipitation. Results: ELISA showed that EGF (10 ng/ml, 18 hr) increased IL-6 secretion (from 234 ± 35 to 923 ± 494 pg/ml, n = 5, p > 0.05), and significantly enhanced BK-induced IL-6 secretion (from 4383 ± 296 to 8312 ± 1267 pg/ml, n = 5, p <0.05) in ASM. Moreover, AG-1478 (2 μM), reduced BK-induced IL-6 secretion by 28% and abrogated the synergic induction of IL-6 induced by BK plus EGF (from 8312 ± 1267 to 3229 ± 597 pg/ml, n = 5, p <0.05). AG-1478 dual effects on IL-6 secretion induced by BK alone or BK plus EGF were also observed in cells treated with genistein, a tyrosine kinase inhibitor, and AG-825, an ErbB-2 inhibitor. Immunoblot analysis demonstrated that AG-1478 had no effect on ERK1/2 activation by BK (1 μM, 10 min). Immunoprecipitation studies showed that BK (1 μM for 2, 5 and 10 min) did not directly transactivate EGFR phosphorylation. Conclusion: These data show that BK and EGF act in concert to regulate the expression of IL-6 in ASM cells possibly via transcriptional mechanisms involving EGFR-associated key signaling molecules.

Original languageEnglish
Pages (from-to)92-99
Number of pages8
JournalChang Gung Medical Journal
Volume33
Issue number1
Publication statusPublished - Jan 2010
Externally publishedYes

Keywords

  • Airway smooth muscle
  • Bradykinin
  • EGF
  • EGF receptor
  • IL-6

ASJC Scopus subject areas

  • Medicine(all)

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