Abstract
BACKGROUND—Eosinophils are thought to play a major role in the pathogenesis of corneal lesions in ocular allergies. The regulation of chemokine production in corneal cells by the Th2 cytokine, interleukin 4 (IL-4), was examined in order to investigate its role in ocular allergies. METHODS—Pure cultures of human corneal epithelial cells and keratocytes were exposed to tumour necrosis factor α (TNF-α) and/or IL-4. 24 hours after exposure, culture supernatants were removed and concentrations of IL-8 and RANTES were quantified by ELISA assay. RESULTS—Simultaneous addition of IL-4 inhibited TNF-α induced IL-8 production in both corneal epithelial cells and keratocytes. TNF-α and IL-4 synergistically stimulated the production of RANTES in keratocytes. CONCLUSION—Differential regulation of chemokine production from corneal cells by IL-4 may play a role in the selective recruitment of predominantly eosinophils to the ocular surface in ocular allergies.
Full Text
The Full Text of this article is available as a PDF (81.4 KB).
Figure 1 .
IL-8 production by corneal epithelial cells (A) and keratocytes (B) (n=3 in triplicate). Cells were stimulated with TNF-α, IL-4, and TNF-α and IL-4 simultaneously. IL-8 was measured in 24 hour cell supernatants by ELISA. In the corneal epithelium, TNF-α induced IL-8 production (p=0.0001 compared with spontaneous release). Simultaneous stimulation with TNF-α and IL-4 resulted in the inhibition of TNF-α induced IL-8 production ( p=0.0002). Stimulation with IL-4 alone produced no significant effect on IL-8 production. In keratocytes, TNF-α induced IL-8 production (p=0.025 compared with spontaneous release). Simultaneous stimulation with TNF-α and IL-4 resulted in the inhibition of TNF-α induced IL-8 production (p=0.039). Stimulation with IL-4 alone produced no significant effect on IL-8 production. Each column and bar represents mean and standard error.
Figure 2 .
RANTES production by corneal epithelial cells (A) and keratocytes (B) (n=3 in triplicate). Cells were stimulated with TNF-α, IL-4, and TNF-α and IL-4 simultaneously. RANTES was measured in 24 hour cell supernatants by ELISA. In corneal epithelium, simultaneous stimulation with TNF-α and IL-4 produced an increase in RANTES production but was not statistically significant (p=0.066 compared with TNF-α alone). In keratocytes, simultaneous stimulation with TNF-α and IL-4 produced an increase in RANTES production compared with TNF-α induced RANTES production (p=0.015 compared with spontaneous release; p=0.020 compared with TNF-α stimulation alone) Stimulation with IL-4 alone produced no significant effect on RANTES production. Each column and bar represents mean and standard error.
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baggiolini M., Dahinden C. A. CC chemokines in allergic inflammation. Immunol Today. 1994 Mar;15(3):127–133. doi: 10.1016/0167-5699(94)90156-2. [DOI] [PubMed] [Google Scholar]
- Bradding P., Roberts J. A., Britten K. M., Montefort S., Djukanovic R., Mueller R., Heusser C. H., Howarth P. H., Holgate S. T. Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol. 1994 May;10(5):471–480. doi: 10.1165/ajrcmb.10.5.8179909. [DOI] [PubMed] [Google Scholar]
- Cubitt C. L., Tang Q., Monteiro C. A., Lausch R. N., Oakes J. E. IL-8 gene expression in cultures of human corneal epithelial cells and keratocytes. Invest Ophthalmol Vis Sci. 1993 Oct;34(11):3199–3206. [PubMed] [Google Scholar]
- Fujishima H., Takeuchi T., Shinozaki N., Saito I., Tsubota K. Measurement of IL-4 in tears of patients with seasonal allergic conjunctivitis and vernal keratoconjunctivitis. Clin Exp Immunol. 1995 Nov;102(2):395–398. doi: 10.1111/j.1365-2249.1995.tb03796.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fukagawa K., Saito H., Tsubota K., Shimmura S., Tachimoto H., Akasawa A., Oguchi Y. RANTES production in a conjunctival epithelial cell line. Cornea. 1997 Sep;16(5):564–570. [PubMed] [Google Scholar]
- Gundel R., Lindell D., Harris P., Fournel M., Jesmok G., Gerritsen M. E. IL-4 induced leucocyte trafficking in cynomolgus monkeys: correlation with expression of adhesion molecules and chemokine generation. Clin Exp Allergy. 1996 Jun;26(6):719–729. [PubMed] [Google Scholar]
- Kung T. T., Stelts D., Zurcher J. A., Jones H., Umland S. P., Kreutner W., Egan R. W., Chapman R. W. Mast cells modulate allergic pulmonary eosinophilia in mice. Am J Respir Cell Mol Biol. 1995 Apr;12(4):404–409. doi: 10.1165/ajrcmb.12.4.7695919. [DOI] [PubMed] [Google Scholar]
- Marfaing-Koka A., Maravic M., Humbert M., Galanaud P., Emilie D. Contrasting effects of IL-4, IL-10 and corticosteroids on RANTES production by human monocytes. Int Immunol. 1996 Oct;8(10):1587–1594. doi: 10.1093/intimm/8.10.1587. [DOI] [PubMed] [Google Scholar]
- Standiford T. J., Strieter R. M., Chensue S. W., Westwick J., Kasahara K., Kunkel S. L. IL-4 inhibits the expression of IL-8 from stimulated human monocytes. J Immunol. 1990 Sep 1;145(5):1435–1439. [PubMed] [Google Scholar]
- Tran M. T., Tellaetxe-Isusi M., Elner V., Strieter R. M., Lausch R. N., Oakes J. E. Proinflammatory cytokines induce RANTES and MCP-1 synthesis in human corneal keratocytes but not in corneal epithelial cells. Beta-chemokine synthesis in corneal cells. Invest Ophthalmol Vis Sci. 1996 May;37(6):987–996. [PubMed] [Google Scholar]
- Trocmé S. D., Hallberg C. K., Gill K. S., Gleich G. J., Tyring S. K., Brysk M. M. Effects of eosinophil granule proteins on human corneal epithelial cell viability and morphology. Invest Ophthalmol Vis Sci. 1997 Mar;38(3):593–599. [PubMed] [Google Scholar]
- Trocmé S. D., Kephart G. M., Bourne W. M., Buckley R. J., Gleich G. J. Eosinophil granule major basic protein deposition in corneal ulcers associated with vernal keratoconjunctivitis. Am J Ophthalmol. 1993 May 15;115(5):640–643. doi: 10.1016/s0002-9394(14)71463-1. [DOI] [PubMed] [Google Scholar]