Cloning and characterization of the guinea pig neutrophil cationic peptide-1 and -2 genes.

Guinea pig neutrophils contain the antimicrobial cationic peptides GNCP-1 and GNCP-2 in the granules. Using cDNA probes, four different GNCP gene clones were isolated from a guinea pig genomic library. Two clones encoded GNCP-1 and other two clones encoded GNCP-2. The nucleotide sequence of GNCP-1 and GNCP-2 gene clones were highly homologous (> 97%) in the region sequenced. The GNCP-1 and GNCP-2 genes spanned 3 kb, and consisted of three exons and two introns. Exon 1 encoded the 5' untranslated region, exon 2 encoded the prepro-peptide region, and exon 3 encoded the mature peptide region and the 3' untranslated region. The transcription start site was located to a thymidine residue 93 bp upstream of the start codon (ATG) of GNCP-1 or GNCP-2 mRNA, and TATA-like sequence was located 24 to 30 bp upstream of the transcription start site. Glucocorticoid regulating element-like sequence was found in the 5' flanking region of the GNCP-1 or GNCP-2 gene, and the GNCP gene transcription rate of bone marrow cells was upregulated by dexamethasone treatment. Together these observations indicate that GNCP-1 and GNCP-2 are encoded by the very homologous but different genes, and that GNCP gene expression is regulated by glucocorticoid.