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- W2021193191 abstract "We previously showed that human corneal epithelial cells (HCECs) express Toll-like receptors (TLRs), which recognize Gram-positive bacteria and respond to Staphylococcus aureus infection by the expression and secretion of proinflammatory cytokines and β-defensin-2 (hBD2). In this study, we further elucidated the underlying mechanisms regulating hBD-2 expression and its role in innate defense in HCECs in response to S. aureus challenge. Exposure of HUCL cells, a telomerase-immortalized HCEC line, to S. aureus, its exoproducts (1:10 dilution), or synthetic lipopeptide Pam3Cys (10 μg/ml) resulted in the up-regulation of hBD-2, but not hBD1 and hBD3. Similar to HUCL cells, primary HCECs responded to S. aureus-exoproducts and Pam3Cys challenge by expressing hBD2 mRNA and secreting hBD2 into the culture media. Furthermore, these stimuli induced the expression of TLR2 at both mRNA and protein levels. Consistently with its role as a major pattern-recognizing receptor, TLR2 was located at the cell surface by cell surface biotinylation. The treatment of HUCL cells with TLR2 neutralizing antibody resulted in a significant decrease in Pam3Cys-induced hBD2 production as well as IL-6, IL-8, and TNF-α secretion. The Pam3Cys-induced hBD2 expression was completely blocked by NF-κB inhibitors and partially inhibited by p38 MAP kinase and the JNK inhibitors. Conditioned media derived from HCECs challenged with S. aureus-exoproducts or Pam3Cys exhibited antibacterial activity against S. aureus, Pseudomonas aeruginosa and Escherichia coli. These findings suggest that S. aureus induces hBD2 production through TLR2-mediated pathways in HCECs and that pathogen-challenged, TLR-activated HCECs possess antimicrobial activity. Thus, the epithelium might play a role in innate defense against bacterial infection by directly killing bacteria in the cornea." @default.
- W2021193191 created "2016-06-24" @default.
- W2021193191 creator A5017947172 @default.
- W2021193191 creator A5033377592 @default.
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- W2021193191 date "2006-02-01" @default.
- W2021193191 modified "2023-09-28" @default.
- W2021193191 title "Toll-like receptor 2-mediated expression of β-defensin-2 in human corneal epithelial cells" @default.
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- W2021193191 doi "https://doi.org/10.1016/j.micinf.2005.07.006" @default.
- W2021193191 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2666383" @default.
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