Title

Human Corneal Epithelial Cells Synthesize ELR−α-Chemokines in Response to Proinflammatory Mediators

Document Type

Article

Publication Title

Ocular immunology and inflammation

Abstract

The purpose of this study was to characterize the synthesis of alpha-chemokines IP-10, MIG, and I-TAC by human corneal epithelial cells (HCE) following exposure to proinflammatory mediators. Supernatants were collected from HCE cultures stimulated with individual or combinations of TNF-alpha, IL-1alpha, and IFN-gamma, and assayed for alpha-chemokines by ELISA. RT-PCR was used to detect IFN-gamma receptor mRNA. Activation of STAT 1 was determined by Western blotting. Stimulation of HCE with either IL-1alpha or TNF-alpha increased IP-10 protein synthesis up to 6-fold, whereas insignificant levels of MIG and I-TAC were induced. The epithelial cells were found to express IFN-gamma receptors constitutively. Exposure to the ligand resulted in STAT 1 phosphorylation and production of nanogram amounts of IP-10, I-TAC, and MIG. When HCE were stimulated with combinations of TNF-alpha and IFN-gamma, or IL-1alpha and IFN-gamma, the levels of IP-10 and I-TAC secreted were > 150-fold higher than that produced following exposure to a single cytokine. In contrast, MIG protein synthesis was not enhanced upon stimulation with cytokine combinations. The abundant production of ELR(-)alpha -chemokines following appropriate stimulation suggests that HCE may play an important role in the recruitment of effector cells such as activated T-lymphocytes to inflamed corneal tissue. The data also indicate that the synthesis of IP-10, I-TAC, and MIG are differentially regulated in HCE.

First Page

295

Last Page

302

DOI

10.1080/09273940701397117

Publication Date

7-1-2007

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