Steroids inhibit vascular endothelial growth factor expression via TLR4/Akt/NF-κB pathway in chronic rhinosinusitis with nasal polyp

Jung Sun Cho, Ju Hyung Kang, Il Ho Park, Heung Man Lee

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Vascular endothelial growth factor (VEGF) is elevated in chronic rhinosinusitis with nasal polyps. Steroids have anti-inflammatory properties and are ideal candidates for treating chronic inflammatory airways. The aims of this study were to identify the inhibitory effects and mechanisms of steroids on lipopolysaccharide (LPS)-induced VEGF expression in nasal polyps. Nasal polyp-derived fibroblasts (NPDFs) were stimulated with LPS alone or with both LPS and steroids were used to determine the expression levels of toll-like receptor (TLR)-4, myeloid differentiation primary response gene 88 (MyD88), and VEGF by using reverse transcription-polymerase chain reaction (RT-PCR). VEGF protein level was analyzed by immunocytochemical staining and enzyme-linked immunosorbent assay (ELISA). Small interfering RNA (siRNA) for TLR4 was transfected to down-regulate TLR4 expression. Activation of Akt and nuclear factor κB (NF-κB) pathway on VEGF expression was determined by Western blot analysis, immunocytochemical staining, and ELISA. Nasal polyp organ cultures were stimulated with LPS alone or in conjunction with steroids or LPS-RS (TLR4 inhibitor) and accessed the expression of VEGF. Steroids decreased the expressions of TLR4, MyD88, and VEGF mRNA and VEGF protein in LPS-stimulated NPDFs. Steroids inhibited LPS-induced VEGF expression levels in dose-dependent manner. The suppression of TLR4 transcription by siRNA treatment reduced LPS-induced expression of both TLR4 and VEGF in NPDFs. Furthermore, steroids inhibited the production of VEGF by blocking Akt and NF-κB activation and preventing with NF-κB translocation. Also, steroid and TLR4 inhibitor decreased VEGF expression in nasal polyp organ cultures. These results indicate that steroids inhibit LPS-induced VEGF expression through the TLR4/Akt/NF-κB signaling pathway in chronic rhinosinusitis with nasal polyp.

Original languageEnglish
Pages (from-to)913-921
Number of pages9
JournalExperimental Biology and Medicine
Issue number8
Publication statusPublished - 2014 Aug 1

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant (no. 2011-0015346) and the Korean Health Technology R&D Project (Ministry of Health & Welfare, no. HI13C1501) funded by the Korea Government and a Korea University Grant.


  • Chronic rhinosinusitis
  • Toll-like receptor 4
  • lipopolysaccharide
  • nasal polyposis
  • steroid
  • vascular endothelial growth factor

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology


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