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标题:Interleukin-32 induced thymic stromal lymphopoietin plays a critical role in the inflammatory response in human corneal epithelium.
时间:2020-03-26 13:12:09
DOI:10.1016/j.cellsig.2018.05.007
PMID:29803543
作者:Lin Jing;Xu Rui;Hu LiTing
出版源: 《Cellular Signalling》 ,49 :39-45
摘要:Interleukin (IL)-32, a novel cytokine, participates in a variety of inflammatory disorders. Thymic stromal lymphopoietin (TSLP) plays important roles in mucosal epithelial cells, especially in allergy-induced inflammation, through the TSLP-TSLPR (thymic stromal lymphopoietin receptor) signalling pathway. However, the association of IL-32 with TSLP on the ocular surface remains unclear. The present work aimed to assess the functional association of IL-32 with TSLP in the control of pro-inflammatory cytokine levels in the corneal epithelium. Human corneal tissue specimens and human corneal epithelial cells (HCECs) were administered different concentrations of IL-32 in the presence or absence of various inhibitors to assess TSLP levels and localization, as well as the molecular pathways that control pro-inflammatory cytokine production. TSLP mRNA levels were determined by real time RT- PCR, while protein levels were quantitated by ELISA and immunohistochemical staining. TSLP protein expression was examined in donor corneal epithelium samples. IL-32 significantly upregulated TSLP and pro-inflammatory cytokines (TNFα and IL-6) in HCECs at the gene and protein levels. The production of pro-inflammatory molecules by IL-32 was increased by recombinant TSLP. Interestingly, both NF-κB (quinazoline) and caspase-1 (VX-765) inhibitors suppressed the IL-32-related upregulation of pro-inflammatory cytokines (TNFα and IL-6). These findings demonstrate that IL-32 and IL-32-induced-TSLP are critical cytokines that participate in inflammatory responses through the caspase-1 and NF-κB signalling pathways in the corneal epithelium, suggesting new molecular targets for inflammatory diseases of the ocular surface. The effects of IL-32 on cell proliferation and apoptosis were investigated by MTT assays and RT-PCR,respectively. The results demonstrated that IL-32 inhibits cells apoptosis in HCECs.
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目录:
  • Interleukin-32 induced thymic stromal lymphopoietin plays a critical role in the inflammatory response in human corneal epithelium
    • Introduction
    • Materials and methods
      • Materials and reagents
      • Ex vivo model of human corneal epithelial tissue for TSLP induction
      • TSLP and inflammatory cytokine induction in the primary human corneal epithelium
      • Caspase-1 enzymatic activity assessment
      • NF-κB signalling evaluation
      • Quantitative RT-PCR
      • Elisa
      • Immunoblot
      • Immunohistochemical staining
      • 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay
        • Statistical analysis
    • Results
      • TSLP production is higher in IL-32-treated HCECs
      • TSLP is upregulated by IL-32 ex vivo in human corneal tissues
      • Caspase-1 is involved in IL-32-associated TSLP upregulation
      • IL-32 mediates pro-inflammatory responses via the caspase-1 and NF-κB pathways in cultured HCECs in vitro
      • TSLP function in IL-32-stimulated inflammatory responses
      • Cell proliferation and apoptosis in IL-32 treated HCECs
    • Discussion
      • Increased TSLP production in IL-32-treated HCECs
      • IL-32 upregulates TSLP via caspase-1 signalling
      • IL-32 mediates inflammatory responses via the caspase-1 and TSLP/NF-κB pathways in cultured HCECs
      • Cell proliferation and apoptosis in IL-32-treated HCECs
    • Contributors
    • Financial interest
    • Funding
    • References

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