15-deoxyprostaglandin-j2 and Lung-Diseases

Multiple factors contribute to the pathogenesis and prognosis of chronic obstructive pulmonary disease(COPD), still requiring new therapeutic strategies and medications for the disease. The aim of the present study is to investigate the model of lipopolysaccharide (LPS)-induced chronic lung injury and hyperinflation and test therapeutic effects of peroxisome proliferator-activated receptor (PPAR)-gamma agonist. Wister rats were challenged with intra-tracheal instillation of LPS at concentrations of 0.006, 0.060, 0.600, and 6.000 mg/ml per kg, twice a week, for 1, 2, 4 and 6 weeks. PPAR activator, 15-deoxy-Delta12,14-prostaglandin J2 (15D-PGJ2), or vehicle (PBS) was administered orally and daily at the dose of 1 and 10 mg/ml per kg in animals challenged with LPS or PBS at the dose of 0.060 mg/ml per kg body weight twice a week for 4 weeks. We found that intra-tracheal exposure of LPS resulted in a dose-dependent pattern of chronic lung hyperinflation and hypertrophy, increased alveolar enlargement, reduced vascular endothelial growth factor (VEGF) and elevated tissue inhibitor of metalloproteinases (TIMP)-1 levels in bronchoalveolar lavage (BAL) fluid, and early changes of leukocyte influx and interferon (IFN)-gamma levels in bronchoalveolar lavage (BAL) fluid. PPAR-gamma agonist ameliorated these changes related with the dose used.LPS-induced lung disease model shows some similarities with human disease, and PPAR-gamma agonist maybe an alternative for COPD therapy.

Topics: Animals; Bronchoalveolar Lavage Fluid; Female; Interferon-gamma; Leukocyte Count; Lipopolysaccharides; Lung; Lung Diseases; Lung Volume Measurements; Pneumonia; PPAR gamma; Prostaglandin D2; Pulmonary Alveoli; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Rats; Rats, Wistar; Tissue Inhibitor of Metalloproteinase-1

A previous study has demonstrated that 15-deoxy-delta12,14-prostaglandin J2 (15d-PG J2) enhanced acute lung injury induced by lipopolysaccharide (LPS) in mice. The enhancement in acute lung injury by 15d-PG J2 was concomitant with the enhanced expression of interleukin-1beta and chemokines in the lung. However, other underlying mechanisms of this enhancement remain to be elucidated. Cyclooxygenase (COX)-2 has been reported to be involved in enhanced pulmonary permeability during acute lung injury. This study investigated the effects of 15d-PG J2 on COXs expressions in the lung in the presence or absence of LPS. ICR mice were divided into 4 experimental groups that intratracheally received vehicle, lipopolysaccharide (LPS: 125 microg/kg), 15d-PG J2 (1 mg/kg), or 15d-PG J2 + LPS. The expression of mRNA for both COX-1 and -2 in the lung was evaluated 4 h after the intratracheal administration. 15d-PG J2 enhanced the COX-2 mRNA expression in the presence of LPS. In contrast, 15d-PG J2 did not affect the COX-1 expression. These results suggest that the enhancing effects of 15d-PG J2 on LPS-induced acute lung injury might be explained, at least in part, by those on the lung expression of COX-2.

Topics: Animals; Bacterial Toxins; Cyclooxygenase 1; Cyclooxygenase 2; Enterotoxins; Escherichia coli Proteins; Isoenzymes; Lipopolysaccharides; Lung; Lung Diseases; Male; Membrane Proteins; Mice; Mice, Inbred ICR; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger