Molecular cloning and in vivo transcriptional expression of rat SLPI in lung inflammation

Proteinase activities have been implicated in a variety of pathogenic processes, including inflammatory lung diseases. The regulation of the activity of serine proteinases such as elastase, trypsin and chymotrypsin secreted by PMN cells during inflammatory lung diseases is important for the prevention of tissue damage. Secretory leukocyte proteinase inhibitor (SLPI) is an inhibitor of these serine proteinases. It is believed that an imbalance between the levels of these proteinases and their inhibitor (SLPI) result in an abnormal degradation of connective tissue, thus suggesting a role for SLPI in the development of lung diseases. To investigate the role of SLPI in lung injury in the rat we have PCR-cloned the gene for rat SLPI and characterized its transcriptional expression. Primers were designed from the known human SLPI sequence. SLPI cDNA was obtained by reverse-transcription-polymerase (RT-PCR) amplification of the corresponding mRNA from lungs of rats injured with IgG immune-complexes. Rat SLPI demonstrates 70% sequence identity with human SLPI at the nucleotide level and 68% identity at the amino acid level. By northern analysis we demonstrate a time dependent increase of rat SLPI message from 0.5 to 8 hours expressed in lungs of rats undergoing IgG immune-complex mediated alvcolitis. There was rapid up-regulation of SLPI mRNA expression beginning at 4 hours and continued increased expression at 6 and 8 hours, suggesting the involvement of SLPI in the development of lung injury.