MOB-1 EXPRESSION IN IL-2-INDUCED ARDS - REGULATION BY TNF-ALPHA

We have recently established an animal model of adult respiratory dist ress syndrome (ARDS)-like microvascular lung injury elicited by infusi on of human interleukin-2 (IL-2). Based on the pronounced, transcripti onal upregulation of multiple pro-inflammatory mediators in IL-2-indue ed ARDS, differential display was applied to search for potentially no vel genes in this paradigm of lung injury. Differential display on tot al lung RNA derived from IL-2-challenged rats presented a highly repro ducible 3'-UTR fragment profile in which a band (approximate to 250 bp ), termed B1, was strongly induced. B1 cDNA sequence exhibited 99.14% homology to the 3'-UTR of mob-1, a recently cloned gene belonging to t he C-X-C chemokine superfamily. Furthermore, Northern blot analysis sh owed that IL-2-induced pulmonary mob-1 mRNA was expressed at time poin ts before the onset of lung injury and suppressed after TNF-alpha inhi bition. These data imply that lung mob-1 is a novel, highly inducible gene in a clinically relevant model of ARDS and, based on its identifi cation as a chemokine, could participate in the development of lung in jury.