| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 From the Departments of Dermatology and 2 Ophthalmology, Emory University School of Medicine, Atlanta, Georgia; the 3 Gillette Medical Evaluation Laboratories, Needham, Massachusetts; and the 4 Veterans Affairs Medical Center, Atlanta, Georgia.
PURPOSE. Gram-negative bacterial infections of the eye can lead to corneal bacterial keratitis, visual impairment, and blindness. Many of these pathologic changes may be mediated by bacterially derived products such as lipopolysaccharide (LPS). In this investigation, it has been established for the first time that human corneal cells are capable of expressing the functional LPS receptor complex proteins, CD14 and Toll-like receptor 4 (TLR4).
METHODS. CD14 and TLR4 mRNA expression in human corneal cells was determined by RT-PCR and Northern blot analysis, and cell surface expression of these proteins was measured by flow cytometry. LPS-mediated corneal cell activation was determined by measuring intracellular calcium mobilization. Cellular cytokine and chemokine secretion in response to LPS was measured by ELISA. The expression and localization of CD14 in whole human cornea was determined by immunohistochemistry.
RESULTS. Human corneal epithelial, stromal, and endothelial cells expressed CD14 mRNA and cell surface CD14. LPS binding to cornea CD14 resulted in a rapid intracellular calcium response and the secretion of multiple proinflammatory cytokines and chemokines. CD14 mRNA expression in corneal epithelial cells was upregulated by LPS. In addition to CD14, corneal epithelial cells expressed the functional LPS receptor–signaling protein TLR4, which was also augmented by LPS.
CONCLUSIONS. The cornea expresses functional CD14 and TLR4 LPS receptor proteins. Understanding the function and biology of the corneal LPS receptor complex may lead to novel therapies for the management of ocular Gram-negative bacterial infections.
This article has been cited by other articles:
|
|
 |
|
  G. Adhikary, Y. Sun, and E. Pearlman C-Jun NH2 terminal kinase (JNK) is an essential mediator of Toll-like receptor 2-induced corneal inflammation J. Leukoc. Biol., April 1, 2008; 83(4): 991 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Johnson, X. Li, and E. Pearlman MyD88 Functions as a Negative Regulator of TLR3/TRIF-induced Corneal Inflammation by Inhibiting Activation of c-Jun N-terminal Kinase J. Biol. Chem., February 15, 2008; 283(7): 3988 - 3996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Du, F. Zhang, J. E. Capo-Aponte, S. D. Tachado, J. Zhang, F.-S. X. Yu, R. A. Sack, H. Koziel, and P. S. Reinach AsialoGM1-Mediated IL-8 Release by Human Corneal Epithelial Cells Requires Coexpression of TLR5 Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4810 - 4818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Huang, W. Du, S. A. McClellan, R. P. Barrett, and L. D. Hazlett TLR4 Is Required for Host Resistance in Pseudomonas aeruginosa Keratitis Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4910 - 4916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Zhang, Z. Liu, and K. E. Meier Lysophosphatidic acid as a mediator for proinflammatory agonists in a human corneal epithelial cell line Am J Physiol Cell Physiol, November 1, 2006; 291(5): C1089 - C1098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Quintar, F. D. Roth, A. L. D. Paul, A. Aoki, and C. A. Maldonado Toll-Like Receptor 4 in Rat Prostate: Modulation by Testosterone and Acute Bacterial Infection in Epithelial and Stromal Cells Biol Reprod, November 1, 2006; 75(5): 664 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Sun, A. G. Hise, C. M. Kalsow, and E. Pearlman Staphylococcus aureus-Induced Corneal Inflammation Is Dependent on Toll-Like Receptor 2 and Myeloid Differentiation Factor 88 Infect. Immun., September 1, 2006; 74(9): 5325 - 5332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Lloyd and P. Kubes GPI-linked endothelial CD14 contributes to the detection of LPS Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H473 - H481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.-S. X. Yu and L. D. Hazlett Toll-like Receptors and the Eye. Invest. Ophthalmol. Vis. Sci., April 1, 2006; 47(4): 1255 - 1263. [Full Text] [PDF]
|
|
|
|
 |
|
 S Rodriguez-Martinez, M E Cancino-Diaz, and J C Cancino-Diaz Expression of CRAMP via PGN-TLR-2 and of {alpha}-defensin-3 via CpG-ODN-TLR-9 in corneal fibroblasts. Br. J. Ophthalmol., March 1, 2006; 90(3): 378 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yamagami, N. Ebihara, T. Usui, S. Yokoo, and S. Amano Bone Marrow-Derived Cells in Normal Human Corneal Stroma Arch Ophthalmol, January 1, 2006; 124(1): 62 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J H Chang, P J McCluskey, and D Wakefield Toll-like receptors in ocular immunity and the immunopathogenesis of inflammatory eye disease Br. J. Ophthalmol., January 1, 2006; 90(1): 103 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Elner, H. R. Petty, V. M. Elner, A. Yoshida, Z.-M. Bian, D. Yang, and A. L. Kindzelskii TLR4 Mediates Human Retinal Pigment Epithelial Endotoxin Binding and Cytokine Expression Invest. Ophthalmol. Vis. Sci., December 1, 2005; 46(12): 4627 - 4633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Huang, R. P. Barrett, S. A. McClellan, and L. D. Hazlett Silencing Toll-like Receptor-9 in Pseudomonas aeruginosa Keratitis Invest. Ophthalmol. Vis. Sci., November 1, 2005; 46(11): 4209 - 4216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Blais, S. G. Vascotto, M. Griffith, and I. Altosaar LBP and CD14 Secreted in Tears by the Lacrimal Glands Modulate the LPS Response of Corneal Epithelial Cells Invest. Ophthalmol. Vis. Sci., November 1, 2005; 46(11): 4235 - 4244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fukuda, N. Kumagai, K. Yamamoto, Y. Fujitsu, N. Chikamoto, and T. Nishida Potentiation of Lipopolysaccharide-Induced Chemokine and Adhesion Molecule Expression in Corneal Fibroblasts by Soluble CD14 or LPS-Binding Protein Invest. Ophthalmol. Vis. Sci., September 1, 2005; 46(9): 3095 - 3101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Rodriguez-Martinez, M E Cancino-Diaz, L Jimenez-Zamudio, E Garcia-Latorre, and J C Cancino-Diaz TLRs and NODs mRNA expression pattern in healthy mouse eye Br. J. Ophthalmol., July 1, 2005; 89(7): 904 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Preciado, E. Caicedo, R. Jhanjee, R. Silver, G. Harris, S. K. Juhn, D. I. Choo, and F. Ondrey Pseudomonas aeruginosa Lipopolysaccharide Induction of Keratinocyte Proliferation, NF-{kappa}B, and Cyclin D1 Is Inhibited by Indomethacin J. Immunol., March 1, 2005; 174(5): 2964 - 2973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chakravarty and M. Herkenham Toll-Like Receptor 4 on Nonhematopoietic Cells Sustains CNS Inflammation during Endotoxemia, Independent of Systemic Cytokines J. Neurosci., February 16, 2005; 25(7): 1788 - 1796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Johnson, F. P. Heinzel, E. Diaconu, Y. Sun, A. G. Hise, D. Golenbock, J. H. Lass, and E. Pearlman Activation of Toll-Like Receptor (TLR)2, TLR4, and TLR9 in the Mammalian Cornea Induces MyD88-Dependent Corneal Inflammation Invest. Ophthalmol. Vis. Sci., February 1, 2005; 46(2): 589 - 595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kumagai, K. Fukuda, Y. Fujitsu, Y. Lu, N. Chikamoto, and T. Nishida Lipopolysaccharide-Induced Expression of Intercellular Adhesion Molecule-1 and Chemokines in Cultured Human Corneal Fibroblasts Invest. Ophthalmol. Vis. Sci., January 1, 2005; 46(1): 114 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ueta, T. Nochi, M.-H. Jang, E. J. Park, O. Igarashi, A. Hino, S. Kawasaki, T. Shikina, T. Hiroi, S. Kinoshita, et al. Intracellularly Expressed TLR2s and TLR4s Contribution to an Immunosilent Environment at the Ocular Mucosal Epithelium J. Immunol., September 1, 2004; 173(5): 3337 - 3347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, H. Li, J. Wang, Z. Dong, S. Mian, and F.-S. X. Yu Role of EGFR Transactivation in Preventing Apoptosis in Pseudomonas aeruginosa-Infected Human Corneal Epithelial Cells Invest. Ophthalmol. Vis. Sci., August 1, 2004; 45(8): 2569 - 2576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Kindzelskii, V. M. Elner, S. G. Elner, D. Yang, B. A. Hughes, and H. R. Petty Toll-Like Receptor 4 (TLR4) of Retinal Pigment Epithelial Cells Participates in Transmembrane Signaling in Response to Photoreceptor Outer Segments J. Gen. Physiol., July 26, 2004; 124(2): 139 - 149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Chang, P. McCluskey, and D. Wakefield Expression of Toll-like Receptor 4 and Its Associated Lipopolysaccharide Receptor Complex by Resident Antigen-Presenting Cells in the Human Uvea Invest. Ophthalmol. Vis. Sci., June 1, 2004; 45(6): 1871 - 1878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Hise, I. Gillette-Ferguson, and E. Pearlman Immunopathogenesis of Onchocerca volvulus keratitis (river blindness): a novel role for TLR4 and endosymbiotic Wolbachia bacteria Innate Immunity, December 1, 2003; 9(6): 390 - 394. [Abstract] [PDF]
|
|
|
|
|
|
J. Zhang, K. Xu, B. Ambati, and F.-S. X. Yu Toll-like Receptor 5-Mediated Corneal Epithelial Inflammatory Responses to Pseudomonas aeruginosa Flagellin Invest. Ophthalmol. Vis. Sci., October 1, 2003; 44(10): 4247 - 4254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. McDermott, R. L. Redfern, B. Zhang, Y. Pei, L. Huang, and R. J. Proske Defensin Expression by the Cornea: Multiple Signalling Pathways Mediate IL-1{beta} Stimulation of hBD-2 Expression by Human Corneal Epithelial Cells Invest. Ophthalmol. Vis. Sci., May 1, 2003; 44(5): 1859 - 1865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Liu, A. A. Roberts, and T. Ganz By IL-1 Signaling, Monocyte-Derived Cells Dramatically Enhance the Epidermal Antimicrobial Response to Lipopolysaccharide J. Immunol., January 1, 2003; 170(1): 575 - 580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Khatri, J. H. Lass, F. P. Heinzel, W. M. Petroll, J. Gomez, E. Diaconu, C. M. Kalsow, and E. Pearlman Regulation of Endotoxin-Induced Keratitis by PECAM-1, MIP-2, and Toll-like Receptor 4 Invest. Ophthalmol. Vis. Sci., July 1, 2002; 43(7): 2278 - 2284. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
