Molecular cloning of the guinea pig GRO gene and its rapid expression in the tissues of lipopolysaccharide-injected guinea pigs

Background: CXC chemokines, IL-8 and GRO, play a role in the recruitment of neutrophils in the human. The functional orthologues in the rat and mouse are CINC/KC and MIP-2. The lack of IL-8 made these animals less useful to study the role of IL-8 and GRO. Methods: Guinea pig (gp) cDNA libraries were screened for GRO and IL-1β. A gp genomic library was screened with a gpGRO cDNA probe. Expression of gpIL-8, gpGRO, gpTNFα, and gpIL-1β was investigated by Northern analysis and/or by in situ hybridization. Results: Two gpGRO cDNAs, a 3.0-kb gpGRO genomic DNA, and a gpIL-1β cDNA were cloned. gpGRO and gpIL-8 mRNA were detected in different tissues including lungs 1 h after intraperitoneal injection of lipopolysaccharide (LPS) into guinea pigs, gpGRO, gpIL-8, gpTNFα, and gpIL-1β expression peaked at 3 h in the lungs. Both gpGRO and gpIL-8 mRNA were detected in the cells in alveolar spaces and bronchial epithelial cells. However, gpGRO mRNA, but not gpIL-8, was also expressed in endothelial cells and vascular smooth muscle cells. Conclusions: gpGRO and gpIL-8 mRNA rapidly accumulated in the lungs of guinea pigs after LPS injection. Expression of gpIL-8 and gpGRO mRNA appeared to be independent from TNFα- or IL-1β-stimulation in this model. A high level expression of gpGRO in vascular cells suggest an important role of GRO in the sequestration of neutrophils and multi-organ injuries induced by LPS. The guinea pig will provide an excellent model to study the roles of IL-8 and GRO, important inflammatory mediators in the human.