Induction of metallothionein and heme oxygenase in rats after inhalation of endotoxin

Various stress proteins appear to play a role in injury and repair produced by inhaled pollutants. The present study examined the effect of inhaled en dotoxin on the expression of the metallothionein and heme oxygenase genes. Rats were exposed to saline or endotoxin aerosols for 3 h and sacrificed up to 3 d following exposure. The significant induction of metallothionein mR NA in both the lung (fourfold increase) and liver (onefold) were greatest a t 3 h and returned to basal levels by 24 h after endotoxin exposure. Simila rly, the increase in tissue metallothionein was greater in the lung. In sit u hybridization in mice showed large increases in the relative abundance of metallothionein transcripts in epithelial cells of the conducting airways, in surrounding airway tissue, and in the nearby gas exchange region. While an endotoxin-induced significant increase in heme oxygenase mRNA followed a time course similar to that observed for metallothionein, the relative ma gnitude was reversed for the lung and liver. Heme oxygenase mRNA war; induc ed greater in the liver (twofold) than in the lung (60% above control). Our findings demonstrate that metallothionein and heme oxygenase are early res ponse genes that are rapidly activated alter inhalation of occupationally r elevant concentrations of endotoxin.