Neopterin-induced expression of intercellular adhesion molecule-1 (ICAM-1)in type II-like alveolar epithelial cells

Production and release of proinflammatory mediators such as tumour necrosis factor-alpha and neopterin are common events following the activation of t he cellular immune system. Concerning inflammatory disorders of the lung, e .g. sepsis or sarcoidosis, high serum neopterin levels have been reported t o correlate well with the severity of the disease. These situations are oft en associated with an increased expression of ICAM-1 reported to be induced in type II alveolar epithelial cells. In our study we investigated the pot ential effects of neopterin on ICAM-1 synthesis in the type II-like pneumoc yte cell line L2. Detection of ICAM-1 gene expression by reverse transcript ase-polymerase chain reaction revealed a dose-dependent effect of neopterin , with maximum impact following 12-h incubations. Comparable results were o btained when ICAM-1 protein synthesis was measured via a cell-based ELISA. In a second set of experiments we were able to show that coincubation of L2 cells with pyrrolidine dithiocarbamate (PDTC) significantly suppressed neo pterin-induced ICAM-1 synthesis. Since PDTC is known to be a potent inhibit or of NF-kappa B, the stimulating effects of neopterin on ICAM-1 gene expre ssion and protein generation may be mediated by activation of this transcri ption factor. From these data we conclude that neopterin stimulates ICAM-1 production in L2 cells. In vivo, these effects may contribute to the prolon gation of the inflammatory response, including cytotoxic cell host defence mechanisms that impair the functions of the airway epithelium.