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

Laurel E. Plummer, Suzette Smiley-Jewell, Kent E Pinkerton

Research output: Contribution to journalArticle

12 Citations (Scopus)

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, exist. TLRs are associated with inflammation and allergy, and emerging evidence suggests they may also play a role in the response and susceptibility to air pollution. However, the specific component, exogenous or endogenous, responsible for the association between air pollution and TLR activation has yet to be clearly identified. Improved understanding of pulmonary response mechanisms and potential mediators of susceptibility to air pollution, including the role of TLRs, may contribute to a reduction of the health burden of air pollution-induced detriments to lung health. This review provides a background of air pollution, health effects associated with exposure to air pollution, and potential contributors to interindividual variability, with a specific focus on TLRs as potential modulators of the immune response.

Original languageEnglish (US)
Pages (from-to)43-57
Number of pages15
JournalInternational Journal of Interferon, Cytokine and Mediator Research
Volume4
Issue number1
StatePublished - Jun 25 2012

Fingerprint

Toll-Like Receptors
Air Pollution
Pneumonia
Air Pollutants
Health
Lung
Innate Immunity
Air
Biological Phenomena
NF-kappa B
Cell Surface Receptors
Adaptive Immunity
Genetic Polymorphisms
Hospital Emergency Service
Immune System
Hypersensitivity
Hospitalization
Oxidative Stress
Transcription Factors

Keywords

  • Air pollution
  • Inflammation
  • Lung
  • Ozone
  • Particulate matter
  • TLR
  • Toll-like receptor

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Impact of air pollution on lung inflammation and the role of toll-like receptors. / Plummer, Laurel E.; Smiley-Jewell, Suzette; Pinkerton, Kent E.

In: International Journal of Interferon, Cytokine and Mediator Research, Vol. 4, No. 1, 25.06.2012, p. 43-57.

Research output: Contribution to journalArticle

@article{ead8dfbc1a3a4763996d6bbcc05072f7,
title = "Impact of air pollution on lung inflammation and the role of toll-like receptors",
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, exist. TLRs are associated with inflammation and allergy, and emerging evidence suggests they may also play a role in the response and susceptibility to air pollution. However, the specific component, exogenous or endogenous, responsible for the association between air pollution and TLR activation has yet to be clearly identified. Improved understanding of pulmonary response mechanisms and potential mediators of susceptibility to air pollution, including the role of TLRs, may contribute to a reduction of the health burden of air pollution-induced detriments to lung health. This review provides a background of air pollution, health effects associated with exposure to air pollution, and potential contributors to interindividual variability, with a specific focus on TLRs as potential modulators of the immune response.",
keywords = "Air pollution, Inflammation, Lung, Ozone, Particulate matter, TLR, Toll-like receptor",
author = "Plummer, {Laurel E.} and Suzette Smiley-Jewell and Pinkerton, {Kent E}",
year = "2012",
month = "6",
day = "25",
language = "English (US)",
volume = "4",
pages = "43--57",
journal = "International Journal of Interferon, Cytokine and Mediator Research",
issn = "1179-139X",
publisher = "Dove Medical Press Ltd.",
number = "1",

}

TY - JOUR

T1 - Impact of air pollution on lung inflammation and the role of toll-like receptors

AU - Plummer, Laurel E.

AU - Smiley-Jewell, Suzette

AU - Pinkerton, Kent E

PY - 2012/6/25

Y1 - 2012/6/25

N2 - 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, exist. TLRs are associated with inflammation and allergy, and emerging evidence suggests they may also play a role in the response and susceptibility to air pollution. However, the specific component, exogenous or endogenous, responsible for the association between air pollution and TLR activation has yet to be clearly identified. Improved understanding of pulmonary response mechanisms and potential mediators of susceptibility to air pollution, including the role of TLRs, may contribute to a reduction of the health burden of air pollution-induced detriments to lung health. This review provides a background of air pollution, health effects associated with exposure to air pollution, and potential contributors to interindividual variability, with a specific focus on TLRs as potential modulators of the immune response.

AB - 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, exist. TLRs are associated with inflammation and allergy, and emerging evidence suggests they may also play a role in the response and susceptibility to air pollution. However, the specific component, exogenous or endogenous, responsible for the association between air pollution and TLR activation has yet to be clearly identified. Improved understanding of pulmonary response mechanisms and potential mediators of susceptibility to air pollution, including the role of TLRs, may contribute to a reduction of the health burden of air pollution-induced detriments to lung health. This review provides a background of air pollution, health effects associated with exposure to air pollution, and potential contributors to interindividual variability, with a specific focus on TLRs as potential modulators of the immune response.

KW - Air pollution

KW - Inflammation

KW - Lung

KW - Ozone

KW - Particulate matter

KW - TLR

KW - Toll-like receptor

UR - http://www.scopus.com/inward/record.url?scp=84864083955&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864083955&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:84864083955

VL - 4

SP - 43

EP - 57

JO - International Journal of Interferon, Cytokine and Mediator Research

JF - International Journal of Interferon, Cytokine and Mediator Research

SN - 1179-139X

IS - 1

ER -