Synergistic effect of TNF-α and IL-4 on the expression of thymus- and activation-regulated chemokine in human corneal fibroblasts

Chemokine production by resident fibroblasts contributes to the recruitment of migratory leukocytes to sites of tissue injury, The effects of cytokines on the expression of thymus- and activation-regulated chemokine (TARC), a potent chemoattractant for Th2 cells, were examined in cultured human corneal fibroblasts. The culture supernatants of cells incubated for 24 h in the absence or presence of either TNF-alpha (10 ng/ml) or IL-4 (10 ng/ml) alone did not contain TARC detectable by ELISA, However, exposure of cells to both cytokines resulted in marked release of TARC into the culture medium in a time- and dose-dependent manner. Similarly, quantitative RT-PCR analysis revealed that the two cytokines induced a synergistic increase in the amount of TARC mRNA in the cultured fibroblasts. This synergistic effect of TNF-a and IL-4 on TARC production by fibroblasts may contribute to the Th2 cell inflammation and consequent tissue damage associated with allergic inflammation. (C) 2000 Academic Press.