Suppressed pulmonary expression of leptin in lipopolysaccharide-induced acute and chronic lung inflammation

Abstract

Leptin, originally described as an adipocyte-derived hormone regulating energy expenditure, is now classified as a type I cytokine. We and others recently demonstrated that the lung is an additional source of leptin. The aim of the present study was to investigate the effect of acute and chronic inflammation on pulmonary expression of leptin in male Swiss mice. Acute lung inflammation was induced by a single intratracheal (IT) dose of 5 µg LPS (E.coli O55:B5), and mice were killed 4h, 24h and 72h postexposure. Chronic lung inflammation was induced by repeated LPS exposure (twice a week for 12 wks) and mice were killed after a 1-wk or 8-wks recovery period. Lungs were removed to assess cellular influx, leptin protein (immunohistochemistry) and mRNA (RT-PCR). Acute LPS exposure induced a transient neutrophilia (Vernooy, J. et al. AJRCMB 2001; 24:569–576). Chronic LPS exposure resulted in persistent accumulation of macrophages and CD8+ T-cells and emphysema (Vernooy, J. et al. AJRCMB 2002; 26:152–159). Control mice displayed positive leptin staining in bronchiolar epithelium and alveolar macrophages. Both acute (4h, 24h, 72h) and chronic (1-wk) inflammation was associated with complete suppression of pulmonary leptin expression at protein and mRNA level. Leptin expression was fully restored after 8-wks of recovery. Lungs of mice displayed constitutive leptin expression in bronchiolar epithelium and alveolar macrophages. Acute and chronic lung inflammation resulted in complete suppression of pulmonary leptin expression. Our data suggest that downregulation of leptin expression in lung may contribute to chronic pulmonary inflammation.