Lipopolysaccharide induces pro-inflammatory cytokines and mmp production via TLR4 in nasal polyp-derived fibroblast and organ culture

Jung Sun Cho, Ju Hyung Kang, Ji Young Um, In Hye Han, Il Ho Park, H. Heung, Lee

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Nasal polyposis is characterized by persistent inflammation and remodeling in sinonasal mucosa. Toll-like receptors (TLRs) play a role in the innate immune response to microbes in the sinonasal cavity. The aim of this study was to evaluate whether nasal polyp-derived fibroblasts (NPDFs) and organ-cultured nasal polyps can synthesize pro-inflammatory cytokines and matrix metalloproteinases (MMPs) after exposure to lipopolysaccharide (LPS), a TLR4 agonist. NPDFs and organ-cultured nasal polyps were isolated from nasal polyps of 8 patients and exposed to LPS. The mRNA and protein expression levels of TLRs, cytokines, and MMPs were determined using a gene expression microarray, real-time RT-PCR, western blot analysis, enzyme-linked immunosorbent assay, and immunofluorescence staining. The enzymatic activities of MMPs were analyzed using collagen or gelatin zymography. The protein expression level of MMP-1 increased in nasal polyp tissues compared to inferior turbinate tissues. LPS induced mRNA expression of TLR4, IL-6, IL-8, and MMP-1 and activated MAPK signaling in NPDFs. LPS promoted the release of interleukin (IL)-6 through extracellular signal-related kinase (ERK) and IL-8 through ERK and c-Jun N-terminal kinases (JNK). Production of IL-6 and IL-8 was induced by PI3K/Akt signaling in LPS-stimulated NPDFs. LPS increased the transcript and protein expression levels of MMP-1 and induced collagenase activity of MMP-1 via ERK and p38, but did not induce gelatinase activity of MMP-2 and MMP-9. LPS from Rhodobacter sphaeroides (LPS-RS) inhibited the stimulatory effects of LPS in NPDFs as well as in organ culture of nasal polyp. LPS triggers immune response via TLR 4 and activates MAPK and PI3K/Akt signaling pathway, which is involved in remodeling of nasal polyps.

Original languageEnglish
Article numbere90683
JournalPLoS One
Volume9
Issue number11
DOIs
Publication statusPublished - 2014 Nov 12

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Nasal Polyps
organ culture
Organ Culture Techniques
Fibroblasts
Cell culture
lipopolysaccharides
fibroblasts
Lipopolysaccharides
cytokines
Cytokines
Matrix Metalloproteinase 1
interstitial collagenase
Matrix Metalloproteinases
Interleukin-8
Interleukin-6
interleukin-8
metalloproteinases
Toll-Like Receptors
interleukin-6
Phosphatidylinositol 3-Kinases

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Lipopolysaccharide induces pro-inflammatory cytokines and mmp production via TLR4 in nasal polyp-derived fibroblast and organ culture. / Cho, Jung Sun; Kang, Ju Hyung; Um, Ji Young; Han, In Hye; Park, Il Ho; Heung, H.; Lee.

In: PLoS One, Vol. 9, No. 11, e90683, 12.11.2014.

Research output: Contribution to journalArticle

Cho, Jung Sun ; Kang, Ju Hyung ; Um, Ji Young ; Han, In Hye ; Park, Il Ho ; Heung, H. ; Lee. / Lipopolysaccharide induces pro-inflammatory cytokines and mmp production via TLR4 in nasal polyp-derived fibroblast and organ culture. In: PLoS One. 2014 ; Vol. 9, No. 11.
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