Chymase inhibition as a pharmacological target: a role in inflammatory and functional gastrointestinal disorders?

Chymase has been extensively studied with respect to its role in the pathophysiology of cardiovascular disease, and is notable for its role in the generation of angiotensin II, a mediator crucial in vascular remodelling. However, in more recent years, an association between chymase and several inflammatory diseases, including gastrointestinal (GI) disorders such as inflammatory bowel diseases (IBD) have been described. Such studies, to date, with respect to IBD at least, are descriptive in the clinical context; nonetheless, preclinical studies implicate chymase in the pathogenesis of gut inflammation. However, studies to elucidate the role of chymase in functional bowel disease are in their infancy, but suggest a plausible role for chymase in contributing to some of the phenotypic changes observed in such disorders, namely increased epithelial permeability. In this short review, we have summarized the current knowledge on the pathophysiological role of chymase and its inhibition with reference to inflammation and tissue injury outside of the GI tract and discussed its potential role in GI disorders. We speculate that chymase may be a novel therapeutic target in the GI tract, and as such, inhibitors of chymase warrant preclinical investigation in GI diseases.

Purification and analysis of a polydnavirus gene product expressed using a poly-histidine baculovirus vector.

The VHv1.1 polydnavirus gene has been implicated in suppressing the encapsulation response in parasitized insects [Li and Webb (1994) J. Virol. 68, 7482-7489]. In order to characterize this gene product and to further our analysis of its immunosuppressive function, we expressed the VHv1.1 using a custom-designed C-terminal poly-histidine baculovirus vector which allows for high expression and single-step purification of the protein. The 34 kDa VHv1.1 protein was expressed in baculovirus-infected cell cultures and in H. virescens larvae. Highly enriched preparations of the secreted VHv1.1 protein were obtained after affinity chromatography using a NTA-(Ni2+) resin. Characterization with purified preparations of the VHv1.1 protein established that the protein is N-glycosylated, containing glycogroups which are PNGase F-sensitive but Endo H-resistant. The recombinant VHv1.1 protein bound to hemocytes in vitro and in vivo and was endocytosed in a manner similar to the native protein produced in CsPDV-infected larvae.