IL-4 and IFNgamma modulate the espression of secretory leukocyte protease inhibitor(SLPI) on A549 human lung adenocarcinoma cell line

COSTA, M; TATEOSIAN, NANCY; BARRO, A; CHULUYAN, E; MAZZEI, A

Congreso; American Thoracic Society Annual Meeting 2007; 2006

American Toracic Society

Secretory leukocyte protease inhibitor (SLPI) is a serpin of 11,7 kDa and it belongs to the family of four disulfide core proteins characterized by whey acid protein (WAP) motif. This protease has been shown to inhibit human neutrophil elastase, trypsin, cathepsin G and chymiotrypsin. SLPI prevents potential injurious effects of proteolytic enzymes released from inflammatory cells. The gene encoding SLPI seems to be modulated at both transcriptional and translational levels, by proinflammatory cytokines such as IL-1 and TNFƒÑ. The aim of this work was to study the modulation of the expression of SLPI by IFNƒ× and IL-4 cytokines, which are produced during a Th1 and Th2 adaptative immune responses, respectively. For this purpose, monolayers of A549 cell line as an in vitro model of Type II alveolar epithelium were treated with IL-4 (20-0.0002 ng/ml) or IFNƒ× (20-0.0002 ng/ml) for 2-16 h. Following, the supernatant was removed and total RNA was extracted from cells to perfom RT-PCR.  The transcriptional level of SLPI on A549, was increased by around 50 % at 30 min but not at 16 h either for IL-4 and IFNƒ×. The expression of SLPI in the supernatant of IL-4 or IFNƒ×-treated cells (16 h, 37¢XC) was also quantified by ELISA. Results showed that IL-4 and IFNƒ× caused a dose-dependent decrease of SLPI, with a threshold IL-4 concentration of 0.2 pg/ml and 20 pg/ml for IFNƒ×. These results indicate that IL-4 and IFNƒ× may be a significant local regulatory signal for SLPI secretion on epithelial cells during an adaptative Th1 and Th2 immune responses.