Quantification of All-Trans Retinoic Acid and Cytokine Levels After Fungal, Viral and Bacterial Infections in the Lung

Abstract

All-trans retinoic acid (atRA) plays a critical role in tissue homeostasis as a master regulator of cellular proliferation, apoptosis and differentiation as well as in immune cell differentiation and function. An active metabolite of vitamin A, atRA has been reported to be reduced in a number of inflammatory conditions in both the lung and gut. Decreases in atRA have been reported in gastrointestinal tissue in inflammatory bowel diseases, radiation-induced gastrointestinal injury and viral infection. In the lung, atRA is reduced in inflammatory conditions including allergic asthma and radiation-induced lung injury; however, the impact of infection on lung atRA is not well defined. In this short communication, we quantified atRA and cytokine levels in the lung after fungal, viral and bacterial infections in mice and determined the correlation between atRA and cytokine levels in the lung. atRA was quantified by LC-MRM³, and seven different inflammatory cytokines were quantified by multiplexed immunoassay in mouse lung challenged with Influenza A, Aspergillus fumigatus, Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. Combined infections were also investigated. Our results show that there is a significant decrease in atRA after infection regardless of infection type. We show an inverse correlation between the decrease in atRA and the increase in inflammatory cytokines IL-1β, IL-6, IL-10 and IL-12 in lung tissue during infection. Elucidation of the homeostatic regulation of active metabolite atRA is important to understanding disease pathology and may enable future drug development to combat the effects of inflammation and infection.