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

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

Research output: Contribution to journalArticle

8 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 1

Fingerprint

Nasal Polyps
Vascular Endothelial Growth Factor A
Lipopolysaccharides
Rhodobacter sphaeroides
Western Blotting
Organ Culture Techniques
Fibroblasts
Enzyme-Linked Immunosorbent Assay
Odontoblasts
Turbinates
Messenger RNA
Proteins
Nasal Mucosa
p38 Mitogen-Activated Protein Kinases
Nose

Keywords

  • Fibroblasts
  • LPS
  • Nasal polyposis
  • TLR
  • VEGF

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Activation of TLR4 induces VEGF expression via Akt pathway in nasal polyps. / Cho, J. S.; Kang, J. H.; Han, I. H.; Um, J. Y.; Lee, Heung Man.

In: Clinical and Experimental Allergy, Vol. 43, No. 9, 01.09.2013, p. 1038-1047.

Research output: Contribution to journalArticle

Cho, J. S. ; Kang, J. H. ; Han, I. H. ; Um, J. Y. ; Lee, Heung Man. / Activation of TLR4 induces VEGF expression via Akt pathway in nasal polyps. In: Clinical and Experimental Allergy. 2013 ; Vol. 43, No. 9. pp. 1038-1047.
@article{5668ff4ead3847c8b8058323ed29ceef,
title = "Activation of TLR4 induces VEGF expression via Akt pathway in nasal polyps",
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.",
keywords = "Fibroblasts, LPS, Nasal polyposis, TLR, VEGF",
author = "Cho, {J. S.} and Kang, {J. H.} and Han, {I. H.} and Um, {J. Y.} and Lee, {Heung Man}",
year = "2013",
month = "9",
day = "1",
doi = "10.1111/cea.12165",
language = "English",
volume = "43",
pages = "1038--1047",
journal = "Clinical and Experimental Allergy",
issn = "0954-7894",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Activation of TLR4 induces VEGF expression via Akt pathway in nasal polyps

AU - Cho, J. S.

AU - Kang, J. H.

AU - Han, I. H.

AU - Um, J. Y.

AU - Lee, Heung Man

PY - 2013/9/1

Y1 - 2013/9/1

N2 - 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.

AB - 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.

KW - Fibroblasts

KW - LPS

KW - Nasal polyposis

KW - TLR

KW - VEGF

UR - http://www.scopus.com/inward/record.url?scp=84882784912&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84882784912&partnerID=8YFLogxK

U2 - 10.1111/cea.12165

DO - 10.1111/cea.12165

M3 - Article

VL - 43

SP - 1038

EP - 1047

JO - Clinical and Experimental Allergy

JF - Clinical and Experimental Allergy

SN - 0954-7894

IS - 9

ER -