Impact of air pollution on lung inflammation and the role of Toll-like receptors

ct of air pollution on lung inflammation and the role of Toll-like receptors Review (1580) Total Article Views Authors: Plummer LE, Smiley-Jewell S, Pinkerton KE Published Date June 2012 Volume 2012:4 Pages 43 - 57 DOI: http://dx.doi.org/10.2147/IJICMR.S29352 Received: 20 December 2011 Accepted: 05 May 2012 Published: 26 June 2012 Laurel E Plummer, Suzette Smiley-Jewell, Kent E Pinkerton Center for Health and the Environment, University of California, Davis, CA, USA Abstract: The link between air pollution and adverse pulmonary health effects is well established. The National Ambient Air Quality Standards were formulated to protect human health. These standards are strictly enforced based on strong associations between elevated air pollution levels and increased emergency room visits and hospitalizations due to respiratory conditions. Impacts of air pollution on lung health occur due to the direct interaction between the external environment and internal biological systems and processes. The innate immune system is one of the first lines of defense against inhaled air contaminants and is characterized by activation of key signaling pathways and inflammatory cell recruitment to the lung. Numerous independent and often redundant pathways participate in innate and adaptive immune responses. Given the impact of air pollution on human health, extensive research efforts have aimed to characterize the mechanisms of response to various air pollutants and evaluate risk factors contributing to individual susceptibility. A significant body of evidence exists to document air pollution–induced alterations in proinflammatory or oxidative signaling molecules. However, the role of specific pathways participating in the propagation of the inflammatory effects remains unclear. One hypothesis for interindividual susceptibility to inhaled air pollutants is that genetic polymorphisms in inflammatory or oxidative stress pathways may contribute to the diverse range of the inflammatory response. Activation of numerous receptors associated with airway cells culminates in the translocation of nuclear factor-kappa B and other transcription factors to the nucleus, and therefore initiation of altered signaling of proinflammatory mediators. Alterations in the transcription and expression of inflammatory mediators following exposure to air pollution are well documented. However, the interaction between specific air pollutants and specific cell surface and intracellular receptors has not been clearly defined. Involvement of specific pathways in the innate immune response may be dependent on differential physical and chemical characteristics of air pollution. One pathway implicated in the response to inhaled air pollutants is initiated by the activation of Toll-like receptors (TLRs). TLRs and downstream proinflammatory mediators are well studied for their role in pathogen response, yet gaps in the understanding of TLR response to nonpathogenic agents, such as air pollution, exis