Pulmonary expression of Pla2g5 during lung damage in mice induced by fipronil and lipopolysaccharide interaction

Abstract

With Indian pesticide industry touching new heights each year in terms of production and sale, its ill effects on health cannot just be ignored. Humans, as well as animals, are under the constant threat of being exposed to environmental pollutants like endotoxins and pesticides which are present ubiquitously in our surroundings. Phenylpyrazoles like fipronil were introduced into the Indian market with an aim to oversee the menace of insecticide resistance and public health hazards experienced with more commonly used pesticide but its adverse effects on the pulmonary system are now being reported globally. We reported first data that the Planar cell Polarity (PCP) pathway was the top dysregulated pathway during fipronil induced lung damage. In order to further elucidate the underlying molecular mechanisms, we analysed the data generated by gene expression profiling in lung tissues using biocomputational approaches. We found Eicosanoid signalling as one of the top enriched pathways dysregulated during fipronil and or endotoxin-induced lung inflammation. Global view of genes showed Pla2g5 as top differentially expressed gene with 1.6, 3.9, 1.2, 3.1 and 4.3-folds expression in lipopolysaccharide (LPS), high dose of fipronil (9.5mg/kg) alone or in combination with LPS and low dose of fipronil (4.75 mg/kg) alone or in combination with LPS, respectively which was validated using qPCR and immunohistochemistry. The data suggest a role Pla2g5 to activate eicosanoid signalling in fipronil and or LPS induced lung inflammation in mice.