Lipopolysaccharide Induces Pro-Inflammatory Cytokines and MMP Production via TLR4 in Nasal Polyp-Derived Fibroblast and Organ Culture

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.

High mobility group box‐1 induces pro‐inflammatory signaling in human nucleus pulposus cells via toll‐like receptor 4‐dependent pathway

“…HMGB1 mediated inflammatory signaling occurs through a number of potential receptors, including toll-like receptor (TLR)-4, [14][15][16][17] TLR-2, 15 and receptor for advanced glycation end products (RAGE). 18,19 Stimulation of these receptors has been shown to activate NF-kB pathway, which triggers the production of pro-inflammatory cytokines, such as IL-6 and MMP-1.…”

“…18,19 Stimulation of these receptors has been shown to activate NF-kB pathway, which triggers the production of pro-inflammatory cytokines, such as IL-6 and MMP-1. 4,13,16,20 In IVD, an elevated IL-6 level decreases expression of ECM constituents, aggrecan and Collagen Type II, 2,21 and is associated with the progression of DD 22 and with LBP associated with DD. 23 MMP-1 levels have also been shown to be elevated in lumbar DD patients.…”

Human Lung Fibroblasts Present Bacterial Antigens to Autologous Lung Th Cells

“…Viral infection causes impairment of macrophage phagocytic clearance (4) and epithelial barrier function (5,6), contributing to bacterial spread into the submucosa. Fibroblasts are the next cellular barrier beneath the respiratory epithelium and express the immune activation molecule CD40 (7), produce cytokines such as IL-6 and IL-8 in response to LPS (8), and respond to IFN-g by releasing T cell chemotactic CCL5 (9). Furthermore, studies focused on the skin (10) and synovial joints (11,12) indicate the potential for fibroblasts to activate Th cells directly through Ag presentation, however, this function in lung fibroblasts remains incompletely understood.…”

Anti-inflammatory Effects of Cardamonin in Ovarian Cancer Cells Are Mediated via mTOR Suppression

“…LPS, the endotoxic part of the gram-negative bacteria, is often used to mimic inflammatory conditions in laboratory experiments. LPS combines with Toll-like receptor 4, which then activates the PI3K/Akt pathway [23,24], promoting the production of inflammatory cytokines and inducing unremitting inflammatory activity. In this study, our results showed higher levels of inflammatory cytokines, including TNF-α, IL-6, and IL-8, and nuclear proteins, such as NF-κB p65, when cells were incubated with LPS, indicating that inflammatory conditions were successfully created.…”