Abstract
Purpose:
Pterygium is an ocular surface lesion characterized by proliferation, inflammatory infiltrates, fibrosis, angiogenesis and extracellular matrix remodeling. Epidemiologic studies have linked pterygium formation to various chronic inflammatory insults, which involve activation of NF-κB pathway. The aim of this study is to determine the gene expression profiles of NF-κB signaling target genes after IKK-2 inhibitor treatment.
Methods:
Primary fibroblast cells were cultured from pterygium and uninvolved conjunctiva tissues from the same patient. Pterygium and conjunctiva fibroblast cells were treated with 10um/L IKK-2 inhibitor for 9 hrs. Control cells were treated with 0.02% DMSO. Total RNA were extracted from treated and untreated pterygium and conjunctiva fibroblast cells. RNA was reverse transcribed to cDNA and then loaded in human NF-κB signaling targets RT2 profileTM PCR array. PCR array data were analyzed by SABioscience PCR array data analysis online system.
Results:
Among the 84 NF-κB signaling target genes, the expression of IL-1RN, LTB, CXCL2, PLAU, C3, NR4A2, CCL11, CXCL1, AGT and BCL2A1were up-regulated, while expression of TNFRSF1B, LTA, MAP2K6, CCL5, CSF2, ICAM1, IL6, FASLG, VCAM1were down-regulated in pterygium fibroblast when compared to conjunctiva fibroblast cells. Among the 10 up-regulated genes, expression level of CXCL2, NR4A2 and CXCL1 were reduced by IKK-2 inhibitor treatment in pterygium fibroblast cells, while others remain unchanged. The expression levels of these three transcripts had no significant changes in IKK-2 inhibitor treated conjunctiva fibroblast cells, but IL-1RN and AGT were down-regulated after IKK-2 inhibitor treatment.
Conclusions:
IKK-2 inhibitor treatment could inhibit up-regulated transcripts in pterygium fibroblasts, and at the same time not affect these transcripts in conjunctiva fibroblasts. Our results shed lights on the possibility of using IKK-2 inhibitor to treat or use as adjunct therapy to primary pterygium.
Keywords: 533 gene/expression •
557 inflammation •
503 drug toxicity/drug effects