We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Lipopolysaccharide Induces Pro-Inflammatory Cytokines and MMP Production via TLR4 in Nasal Polyp-Derived Fibroblast and Organ Culture.
- Authors
Cho, Jung-Sun; Kang, Ju-Hyung; Um, Ji-Young; Han, In-Hye; Park, Il-Ho; Lee, Heung-Man
- 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.
- Subjects
NOSE diseases; CYTOKINES; TOLL-like receptors; LIPOPOLYSACCHARIDES; FIBROBLASTS; ORGAN culture; NASAL mucosa; IMMUNE response
- Publication
PLoS ONE, 2014, Vol 9, Issue 11, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0090683