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UVB-Mediated Induction of Cytokines and Growth Factors in Pterygium Epithelial Cells Involves Cell Surface Receptors and Intracellular Signaling

¹From the Inflammatory Diseases Research Unit, Department of Pathology, School of Medical Sciences, University of New South Wales, Sydney, Australia; and the ²Department of Ophthalmology, Prince of Wales Hospital, Sydney, Australia.

PURPOSE. Pterygium is a proliferative, inflammatory, and invasive ocular surface disease associated with excessive ultraviolet (UV) exposure. This investigation was conducted to identify UV activated signaling pathways in pterygium epithelial cells (PECs) that mediate cytokine and growth factor production and to determine whether these pathways are sensitive to blockade by anti-inflammatory agents such as retinoic acid (RA) and interferon (IFN)-.

METHODS PECs were pretreated with or without inhibitors of the ERK1/2, JNK, and p38 (PD98059, SB202190, and SB203580, respectively) mitogen-activated protein kinases (MAPK) or with inhibitors of the tyrosine kinase activity of epidermal growth factor receptor (EGFR; PD153035) and platelet-derived growth factor (PDGF; AG1295); exposed to UVB (20 mJ/cm²); and then further treated with the same inhibitors. Media were harvested and analyzed by ELISA for interleukin (IL)-6, IL-8, and vascular endothelial growth factor (VEGF). Cytokine mRNA was assessed by reverse transcription–polymerase chain reaction (RT-PCR).

RESULTS Inhibitors of ERK1/2, JNK, and p38 MAPKs significantly abolished the UVB-mediated increase in IL-6, IL-8, and VEGF. PD153035 reduced IL-8, AG1295 repressed IL-6, and both inhibitors partially downregulated VEGF production in UV-exposed PECs. RA and IFN- dose dependently abrogated IL-6 and IL-8 but had no effect on VEGF expression after UV exposure.

CONCLUSIONS The results have identified a stress-induced intracellular pathway and potential cell-surface transmitters that may be relevant to pterygium development. Moreover, two anti-inflammatory/antiangiogenic agents were identified that reduced cytokine production in the study model. Topical application of these drugs may benefit patients with pterygia, potentially reducing the necessity for surgical interven-tion.

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