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STRESS IN THE AIR: INHALED POLLUTANTS AND MULTI-ORGAN IMPAIRMENT
Citation:
Kodavanti, U. STRESS IN THE AIR: INHALED POLLUTANTS AND MULTI-ORGAN IMPAIRMENT. 10th Annual Convention of Association of Biotechnology and Pharmacy, Tirupati, INDIA, December 21, 2016.
Impact/Purpose:
This abstract summarizes the involvement of stress response pathway as central mechanism in irritant air pollutant-induced systemic metabolic and pulmonary immune effects.
Description:
Air pollution has been blamed for nearly 7 million premature deaths worldwide. For decades, the research on how air pollution impacts human health has centered on cardiopulmonary consequences. However, more recently it is clearly evident that air pollution affects every organ in the body and contributes to a variety of chronic diseases such as cardiovascular, brain disorders, diabetes and reproductive. It is proposed that multi-organ effects of air pollution are mediated by circulating reactive intermediates released from the lung upon encountering air pollution. Recently, our lab has demonstrated that a different mechanism is central in mediating multi-organ effects. We have shown that air pollution exposure stimulates central hypothalamic regions to activate neuroendocrine sympathetic-adrenal-medullary (SAM) and hypothalamic-pituitary-adrenal (HPA) axes. As a consequence, two fundamental survival processes known to be activated during a physical or psychological stress are induced. Those homeostatic processes - metabolic rearrangement and immune response - engages virtually all organs in the body to harmonize their efforts in producing an array of organ-specific effects known as the classical fight-or-flight response. We propose that perturbation in this response in any given organ is central to increased susceptibility to adverse health effects of pollutants. Our studies using a combination of metabolomic and high-throughput genomic approaches demonstrate that exposure to irritant air pollutants induce an array of metabolic effects in rodents and humans affecting glucose metabolism, insulin release, tissue lipid redistribution and muscle breakdown. We have also shown that two stress hormones, adrenaline and cortisol, released in the circulation after an air pollution exposure mediate not only these metabolic effects, but also an immune response to affect lung injury and inflammation through adrenergic and steroidal receptors. Therapeutically, these outcomes have significant implication in the treatment of chronic diseases since these receptors are widely manipulated in the treatment of chronic inflammatory and metabolic conditions. (This abstract does not necessarily reflect the US EPA policy).