TLR-mediated Induction of Proinflammatory Cytokine IL-32 in Corneal Epithelium

Zhang, Lili; Che, Cheng-Ye; Lin, Jing; Liu, Kuixiang; Li, Dequan; Zhao, Guiqiu

doi:10.3109/02713683.2012.763102

Cited by 14 publications

(15 citation statements)

References 21 publications

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“…D and E). A TLR3‐mediated signal regulates IL‐32 secretion, and IL‐32 induces the production of pro‐inflammatory cytokines . The EBERs‐TLR3 interaction was examined to investigate its effect on IL‐32 production in HCECs/EBV.…”

Section: Resultsmentioning

confidence: 99%

“…Interleukin‐32 is a recently described cytokine produced by T lymphocytes, natural killer cells, epithelial cells, mast cells, keratinocytes and blood monocytes . IL‐32 secretion is modulated by signals transferred from specific TLRs, such as TLR2, TLR3, TLR4, TLR5 and TLR6, in corneal epithelium . IL‐32 also induces the production of pro‐inflammatory cytokines, such as TNF‐α, IL‐1β, IL‐6 and IL‐8 by activating NF‐κB and p38 mitogen‐activated protein kinase (MAPK) .…”

Section: Introductionmentioning

confidence: 99%

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TLR3/TRIF signalling pathway regulates IL‐32 and IFN‐β secretion through activation of RIP‐1 and TRAF in the human cornea

Park

Hur

Kim

et al. 2015

J Cellular Molecular Medi

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Toll-like receptor-3 (TLR3) and RNA helicase retinoic-acid-inducible protein-1 (RIG-I) serve as cytoplasmic sensors for viral RNA components. In this study, we investigated how the TLR3 and RIG-I signalling pathway was stimulated by viral infection to produce interleukin (IL)-32-mediated pro-inflammatory cytokines and type I interferon in the corneal epithelium using Epstein–Barr virus (EBV)-infected human cornea epithelial cells (HCECs/EBV) as a model of viral keratitis. Increased TLR3 and RIG-I that are responded to EBV-encoded RNA 1 and 2 (EBER1 and EBER2) induced the secretion of IL-32-mediated pro-inflammatory cytokines and IFN-β through up-regulation of TRIF/TRAF family proteins or RIP-1. TRIF silencing or TLR3 inhibitors more efficiently inhibited sequential phosphorylation of TAK1, TBK1, NF-κB and IRFs to produce pro-inflammatory cytokines and IFN-β than RIG-I-siRNA transfection in HCECs/EBV. Blockade of RIP-1, which connects the TLR3 and RIG-I pathways, significantly blocked the TLR3/TRIF-mediated and RIG-I-mediated pro-inflammatory cytokines and IFN-β production in HCECs/EBV. These findings demonstrate that TLR3/TRIF-dependent signalling pathway against viral RNA might be a main target to control inflammation and anti-viral responses in the ocular surface.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TLR3/TRIF signalling pathway regulates IL‐32 and IFN‐β secretion through activation of RIP‐1 and TRAF in the human cornea

Park

Hur

Kim

et al. 2015

J Cellular Molecular Medi

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“…In the ocular epithelial tissue, expression of hBD-9 is also induced by TLR2, TLR3, TLR4 and TLR5 signaling (150, 151). In immortalized human eye tissue, mRNA expression and secreted IL-1β, IL-6, IL-8, MCP-1 and sICAM-1, IL-32, IL-33 and TNF-α are induced by TLR2, TLR3, TLR4 and TLR5 signaling in response to viral and bacterial stimulation (91, 94, 96, 152). …”

Section: Tlr Expression and Responses In Human Mucosal Epithelial Tismentioning

confidence: 99%

TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens

2014

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Toll-like receptor (TLR) signaling represents one of the best studied pathways to implement defense mechanisms against invading microbes in human being as well as in animals. TLRs respond to specific microbial ligands and to danger signals produced by the host during infection, and initiate downstream cascades that activate both innate and adaptive immunity. TLRs are expressed by professional immune cells and by the large majority of non-hematopoietic cells, including epithelial cells. In epithelial tissues, TLR functions are particularly important because these sites are constantly exposed to microorganisms, due to their location at the host interface with the environment. While at these sites specific defense mechanisms and inflammatory responses are initiated via TLR signaling against pathogens, suppression or lack of TLR activation is also observed in response to the commensal microbiota. The mechanisms by which TLR signaling is regulated in mucosal epithelial cells include differential expression and levels of TLRs (and their signaling partners), their cellular localization and positioning within the tissue in a fashion that favors responses to pathogens while dampening responses to commensals and maintaining tissue homeostasis in physiologic conditions. In this review, the expression and activation of TLRs in mucosal epithelial cells of several sites of the human body are examined. Specifically, the oral cavity, the ear canal and eye, the airways, the gut, and the reproductive tract are discussed, along with how site-specific host defense mechanisms are implemented via TLR signaling.

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“…FAK-related non-kinase, a peptide with a structure similar to the FAT region, inhibits FAK signal transduction [ 15 ]. Because the integrin-FAK signaling axis is critical for the development of tissue fibrosis [ 16 , 17 ], we predicted that IL-32 interrupts the signaling pathway by binding to these molecules, thereby inhibiting FAK activation and alleviating fibrosis.…”

Section: Introductionmentioning

confidence: 99%

IL-32γ attenuates airway fibrosis by modulating the integrin-FAK signaling pathway in fibroblasts

et al. 2018

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BackgroundFibrosis in severe asthma often leads to irreversible organ dysfunction. However, the mechanism that regulates fibrosis remains poorly understood. Interleukin (IL)-32 plays a role in several chronic inflammatory diseases, including severe asthma. In this study, we investigated whether IL-32 is involved in fibrosis progression in the lungs.MethodsMurine models of chronic airway inflammation induced by ovalbumin and Aspergillus melleus protease and bleomycin-induced pulmonary fibrosis were employed. We evaluated the degree of tissue fibrosis after treatment with recombinant IL-32γ (rIL-32γ). Expression of fibronectin and α-smooth muscle actin (α-SMA) was examined and the transforming growth factor (TGF)-β-related signaling pathways was evaluated in activated human lung fibroblasts (MRC-5 cells) treated with rIL-32γ.ResultsrIL-32γ significantly attenuated collagen deposition and α-SMA production in both mouse models. rIL-32γ inhibited the production of fibronectin and α-SMA in MRC-5 cells stimulated with TGF-β. Additionally, rIL-32γ suppressed activation of the integrin-FAK-paxillin signaling axis but had no effect on the Smad and non-Smad signaling pathways. rIL-32γ localized outside of MRC-5 cells and inhibited the interaction between integrins and the extracellular matrix without directly binding to intracellular FAK and paxillin.ConclusionsThese results demonstrate that IL-32γ has anti-fibrotic effects and is a novel target for preventing fibrosis.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0863-3) contains supplementary material, which is available to authorized users.

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TLR-mediated Induction of Proinflammatory Cytokine IL-32 in Corneal Epithelium

Abstract: These findings demonstrate that IL-32 is induced by microbial ligands through TLR-mediated innate signaling pathways, suggesting an important role of corneal epithelium in inflammatory disease.

Cited by 14 publications

References 21 publications

TLR3/TRIF signalling pathway regulates IL‐32 and IFN‐β secretion through activation of RIP‐1 and TRAF in the human cornea

TLR3/TRIF signalling pathway regulates IL‐32 and IFN‐β secretion through activation of RIP‐1 and TRAF in the human cornea

TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens

IL-32γ attenuates airway fibrosis by modulating the integrin-FAK signaling pathway in fibroblasts

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