Innate Immune Response of Corneal Epithelial Cells to Staphylococcus aureus Infection: Role of Peptidoglycan in Stimulating Proinflammatory Cytokine Secretion
Open accessAbstract
Purpose This study sought to elucidate the innate immune responses of cultured human corneal epithelial cells (HCECs) to infection by the Gram-positive bacterium Staphylococcus aureus and to determine the underlying mechanisms. Methods HUCL, a telomerase-immortalized HCEC line, and primary cultures of HCECs were challenged with live or heat-killed S. aureus, its exoproducts, or cell wall components lipoteichoic acid (LTA) and peptidoglycan (PGN). IkappaB-alpha phosphorylation and degradation as well as phosphorylation of MAPKs, p38, and JNK-1/2, were assessed by Western blot analysis. The expression of interleukin (IL)-6, IL-8, TNF-alpha, and beta-defensin-2 were determined using RT-PCR and secretion of IL-6, IL-8, TNF-alpha, and beta-defensin were measured using enzyme-linked immunosorbent assay and immunoblot analysis of culture medium. Results Exposure of HUCL cells to live, but not heat-killed, S. aureus resulted in NF-kappaB activation in a time-dependent manner, as assessed by the increase in IkappaB-alpha phosphorylation and degradation. Live bacteria also activated the p38 and JNK pathways. The effects of live bacteria on HUCL cells may be attributable to bacterial exoproducts, since the conditioned medium of S. aureus also effectively stimulated these signaling pathways. PGN, but not LTA, activated the NF-kappaB and MAPK pathways in a dose- and time-dependent manner. Concomitant with activation of NF-kappaB and MAPKs, transcriptional expression of IL-6, IL-8, TNF-alp…
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The use of TNF-α as a pro-inflammatory stimulus in the cell culture model has important physiological relevance to corneal inflammation and epithelial wound healing.
“The use of TNF-α as a pro-inflammatory stimulus in our cell culture model has important physiological relevance to corneal inflammation and epithelial wound healing.”
From Thymosin beta 4 suppression of corneal NFκB: A potential anti-inflammatory pathway (2007) · cites this paper as Kumar et al., 2004
TNF-α is increased in tears during infections and inflammations of the cornea.
“This is because TNF-α is increased in tears during infections and inflammations of the cornea, suggesting its importance as a mediator of inflammation in vitro as well as in vivo (Bitko et al., 2004; Kumar et al., 2004; Saika et al., 2005).”
From Thymosin beta 4 suppression of corneal NFκB: A potential anti-inflammatory pathway (2007) · cites this paper as Kumar et al., 2004
Cites
Receptor-Dependent Mechanisms of Cell Stimulation by Bacterial Endotoxin
Ulevitch, R. J., & Tobias, P. S. (1995) · Annual Review of Immunology · doi:10.1146/annurev.iy.13.040195.002253 · Cited by 1,442 · cited 1× · see citing works
“PGN is an alternating -linked N-acetylmuramyl and N-acetylglucosaminyl glycan whose residues are cross-linked by short peptides.(22,23) LTA is anchored in the membrane by glycolipids found in many Gram-positive bacteria(24) and has been shown to induce the ERK signaling pathway in the cornea.”
Melmed, G., Thomas, L. S., Lee, N., Tesfay, S. Y., Lukasek, K., Michelsen, K. S., Zhou, Y., Hu, B., Arditi, M., & Abreu, M. T. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.3.1406 · Cited by 431 · see citing works
Rheinwald, J. G., Hahn, W. C., Ramsey, M. R., Wu, J. Y., Guo, Z., Tsao, H., De Luca, M., Catricalà, C., & O'Toole, K. M. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.14.5157-5172.2002 · Cited by 338 · see citing works
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Thymosin beta 4 suppression of corneal NFκB: A potential anti-inflammatory pathway
Sosne, G., Qiu, P., Christopherson, P. L., & Wheater, M. K. (2007) · Experimental Eye Research · doi:10.1016/j.exer.2006.12.004 · Cited by 139 · see citing works
Wang, L., Reinach, P., & Lu, L. (2005) · Experimental Cell Research · doi:10.1016/j.yexcr.2005.08.020 · Cited by 27 · see citing works
- Authors
- Kumar, A., Zhang, J., & Yu, F.-S. X.
- Affiliations
- Augusta University (US)
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2004-10-01
- Volume
- 45
- Issue
- 10
- Pages
- 3513
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC2666393
- OpenAlex
- W2095344941
- Cited by
- 127
- References
- 3
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 2 · 2019: 3 · 2017: 5 · 2016: 5 · 2015: 11 · 2014: 5 · 2013: 4 · 2012: 6
- FWCI
- 9.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (R01EY014080, EY-10869, R01EY010869, EY14080)
- Topics
- Health Sciences › Medicine › Ophthalmology › Ocular Infections and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- corneal epithelial cells, Staphylococcus aureus, innate immunity, peptidoglycan, lipoteichoic acid, NF-κB activation, MAPK signaling, p38 MAPK, JNK, inflammatory cytokines, interleukin-6, interleukin-8, TNF-α, human beta-defensin 2, Gram-positive bacteria, corneal infection
- MeSH terms
- NF-KappaB Inhibitor alpha, Cells, Cultured, Dose-Response Relationship, Drug, Humans, Immunity, Innate, Lipopolysaccharides, Peptidoglycan, Phosphorylation, RNA, Messenger, Staphylococcus aureus, Teichoic Acids, Time Factors, Blotting, Western, Cytokines, Epithelium, Corneal, Reverse Transcriptase Polymerase Chain Reaction, I-kappa B Proteins, Mitogen-Activated Protein Kinases, beta-Defensins, p38 Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 8
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