Activation of TLR4 induces VEGF expression via Akt pathway in nasal polyps

J. S. Cho, J. H. Kang, I. H. Han, J. Y. Um, H. M. Lee

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Nasal polyposis is characterized by tissue remodelling and oedematous nasal mucosa. Vascular endothelial growth factor (VEGF) plays a significant role in the regulation of remodelling in nasal polyps. TLR4 activation is associated with VEGF expression in murine macrophages and odontoblasts. Objective: This study aimed to evaluate whether lipopolysaccharide (LPS), an inducer of TLR4, stimulates VEGF expression and to determine the mechanism underlying VEGF production in nasal polyps. Methods: Nasal polyp-derived fibroblasts (NPDFs) were isolated from 10 patients with nasal polyps and exposed to LPS. LPS from Rhodobacter sphaeroides (LRS) was used to inhibit the expression levels of TLR4, MyD88 and VEGF. Messenger RNA (mRNA) expression levels of TLRs, MyD88 and VEGF were determined by gene expression microarray and semiquantitative reverse transcription-PCR. Protein expression levels of TLR4 and VEGF were analysed using western blot, immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA). Activation of MAPKs (ERK, p38, and JNK) and Akt was examined using western blot analysis. The expression level of VEGF was measured by ELISA and western blot analysis in ex vivo nasal polyp organ culture. Results: The protein expression level of VEGF was increased in nasal polyp tissues compared with inferior turbinate tissues. LRS inhibited the mRNA and protein expression of TLR4, MyD88 and VEGF in LPS-stimulated NPDFs. LPS-activated MAPKs and Akt signals, whereas MAPK inhibitors did not inhibit VEGF expression, and only Akt inhibitor blocked VEGF production. LRS reduced the production of VEGF in LPS-stimulated ex vivo organ culture. Conclusions and Clinical Relevance: These results suggest that LPS stimulates the production of VEGF through the TLR4-Akt signalling pathway in nasal polyps. LPS may be involved in the pathogenesis of nasal polyp remodelling.

Original languageEnglish
Pages (from-to)1038-1047
Number of pages10
JournalClinical and Experimental Allergy
Volume43
Issue number9
DOIs
Publication statusPublished - 2013 Sep

Keywords

  • Fibroblasts
  • LPS
  • Nasal polyposis
  • TLR
  • VEGF

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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