Inhibitory action of tetrandrine on macrophage production of interleukin-1 (IL-1)-like activity and thymocyte proliferation.
Authors
Kang-JH; Lewis-DM; Castranova-V; Rojanasakul-Y; Banks-DE; Ma-JY; Ma-JK
Source
Exp Lung Res 1992 Sep-Oct; 18(5):715-729
Abstract
Tetrandrine is a bisbenzylisoquinoline alkaloid which has been shown to exhibit antifibrotic activity against silicosis. Tetrandrine is characterized by its strong binding to alveolar macrophages and inhibition of particle-induced respiratory burst activity in these phagocytes. In contrast, tubocurine and tubocurarine are structurally similar to tetrandrine but exhibit little effect on fibrosis or activation of alveolar macrophages. The objective of the present study was to test the effect of tetrandrine on macrophage production of monokines in response to occupational dusts, and to determine tetrandrine's effect on monokine-medicated cell growth using a mouse thymocyte proliferation assay and lipopolysaccharide (LPS) as a positive control. Stimulation of alveolar macrophages by respirable silica dust resulted in a release of monokines which caused a fourfold increase in thymocyte proliferation. Coal dust, on the other hand, had no effect on macrophage production of this cytokine. Tetrandrine was found to exhibit a dose-dependent inhibition of monokine release from both silica and LPS-stimulated alveolar macrophages. In experiments where thymocytes were directly treated with tetrandrine, a dose-dependent inhibition of thymocyte proliferation was noted with both interleukin-1-(IL-1) specific and nonspecific mitogenic (concanavalin A) actions. In contrast to the inhibitory potency of tetrandrine, tubocurarine was found to have no effect on either the production of monokines by LPS-stimulated alveolar macrophages or IL-1-mediated thymocyte proliferation. These results provide a correlation between the antifibrotic effect of tetrandrine and inhibition of macrophage activation.
Keywords
Respiratory-system-disorders; Pulmonary-disorders; Pulmonary-system-disorders; Lung-disorders; Cellular-reactions; Cellular-function; Cell-function; Fibrogenesis; Fibrogenicity; Fibrosis; Therapeutic-agents
Contact
Dr. Joseph K. H. Ma, School of Pharmaq West Virginia University, HSN Morgantown, WV 26506
CAS No.
518-34-3; 14808-60-7
Document Type
Journal Article
Funding Type
Cooperative Agreement; Grant
Identifying No.
Cooperative-Agreement-Number-U60-CCU-306149; 1195142-5430
Source Name
Experimental Lung Research
Performing Organization
Center to Protect Workers' Rights
