Suppressive Effects of Tranilast on Pulmonary Fibrosis and Activation of Alveolar Macrophages in Mice Treated with Bleomycin: Role of Alveolar Macrophages in the Fibrosis

Abstract

ABSTRACT-We have reported that tranilast, an anti-allergic drug that inhibits chemical mediator release from mast cells, suppresses bleomycin (BLM)-induced pulmonary fibrosis in mice through mechanisms other than inhibiting chemical mediator release from mast cells. The purpose of this paper is to examine the effect of tranilast on alveolar macrophage (AM) activation and on the development of fibrosis in ICR mice instilled with BLM intratracheally. Twenty eight days after the BLM instillation (0.01 mg/mouse), AM often migrated into alveolar spaces surrounding the fibrotic areas. Flow cytometry analysis for the size and density of AM (MAC-1 positive cells) suggested that AM were activated not only in the earlier acute inflammatory phase, but also in the later chronic phase. The p.o. administration of tranilast suppressed an increase of AM activity to produce reactive oxygen species in BLM-instilled mice, and it inhibited the subsequent development of pulmonary fibrosis. In vitro treatment with tranilast suppressed the reactive oxygen species production from murine peritoneal macrophages. However, several different anti-oxidants failed to inhibit the development of fibrosis. These results suggest that the activation of AM plays an important role in the development of fibrosis, and it is likely that tranilast suppresses fibrosis by inhibiting AM activation but not by scavenging reactive oxygen species.

Tranilast Suppresses the Disease Development of the Adjuvant- and Streptococcal Cell Wall-Induced Arthritis in Rats

“…It is already well known that tranilast has an inhibitory effect on the development of fibrosis (29,30), and in the two RA models in the present study, tranilast again showed its ability as an anti-fibrotic agent. However, the mechanism for this effect in these models remains unclear, especially with regards to the anti-inflammatory effects of tranilast.…”

The effect of allergen-induced airway inflammation on airway remodeling in a murine model of allergic asthma

“…Whole collagen content of the right lung was evaluated by determining hydroxyproline content [18]. Briefly, after recovery of BALF, the right lung lobes were removed and cut into sections (1 mm thick).…”

Time course study on the development of allergen-induced airway remodeling in mice: the effect of allergen avoidance on established airway remodeling

“…Whole collagen content of the right lung was evaluated by determining hydroxyproline content [15]. Briefly, the right lung was cut into sections (1 mm thick).…”