Lipopolysaccharide induces pro-inflammatory cytokines and MMP production via TLR4 in nasal polyp-derived fibroblast and organ culture.
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.
Brain Korea 21 Plus for Biomedical Science, College of Medicine, Korea University, Seoul, South Korea; Institute for Medical Devices Clinical Trial Center, Korea University, Guro Hospital, Seoul, South Korea.
Jung-Sun
JS
Cho
Brain Korea 21 Plus for Biomedical Science, College of Medicine, Korea University, Seoul, South Korea.
Ju-Hyung
JH
Kang
Brain Korea 21 Plus for Biomedical Science, College of Medicine, Korea University, Seoul, South Korea.
Ji-Young
JY
Um
Brain Korea 21 Plus for Biomedical Science, College of Medicine, Korea University, Seoul, South Korea.
In-Hye
IH
Han
Institute for Medical Devices Clinical Trial Center, Korea University, Guro Hospital, Seoul, South Korea; Department of Otorhinolaryngology-Head and Neck Surgery, Korea University, Guro Hospital, Seoul, South Korea.
Il-Ho
IH
Park
Brain Korea 21 Plus for Biomedical Science, College of Medicine, Korea University, Seoul, South Korea; Institute for Medical Devices Clinical Trial Center, Korea University, Guro Hospital, Seoul, South Korea; Department of Otorhinolaryngology-Head and Neck Surgery, Korea University, Guro Hospital, Seoul, South Korea.
Heung-Man
HM
Lee
D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009298:Nasal Polyps / Q000378:metabolism* / Q000473:pathology; D009924:Organ Culture Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D016207:Cytokines; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020782:Matrix Metalloproteinases