Transient receptor potential (TRP) channels as molecular targets in lung toxicology and associated diseases

Cell Calcium. 2017 Nov;67:123-137. doi: 10.1016/j.ceca.2017.04.005. Epub 2017 Apr 26.


The lungs as the gateways of our body to the external environment are essential for gas exchange. They are also exposed to toxicants from two sides, the airways and the vasculature. Apart from naturally produced toxic agents, millions of human made chemicals were produced since the beginning of the industrial revolution whose toxicity still needs to be determined. While the knowledge about toxic substances is increasing only slowly, a paradigm shift regarding the proposed mechanisms of toxicity at the plasma membrane emerged. According to their broad-range chemical reactivity, the mechanism of lung injury evoked by these agents has long been described as rather unspecific. Consequently, therapeutic options are still restricted to symptomatic treatment. The identification of molecular down-stream effectors in cells was a major step forward in the mechanistic understanding of the action of toxic chemicals and will pave the way for more causal and specific toxicity testing as well as therapeutic options. In this context, the involvement of Transient Receptor Potential (TRP) channels as chemosensors involved in the detection and effectors of toxicant action is an attractive concept intensively discussed in the scientific community. In this review we will summarize recent evidence for an involvement of TRP channels (TRPA1, TRPC4, TRPC6, TRPV1, TRPV4, TRPM2 and TRPM8) expressed in the lung in pathways of toxin sensing and as mediators of lung inflammation and associated diseases like asthma, COPD, lung fibrosis and edema formation. Specific modulators of these channels may offer new therapeutic options in the future and will endorse strategies for a causal, specifically tailored treatment based on the mechanistic understanding of molecular events induced by lung-toxic agents.

Keywords: Acute lung injury (ALI); Asthma; Chronic obstructive pulmonary disease (COPD); Edema; Fibrosis; Lung; Toxicity; Transient receptor potential (TRP) channels.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants / toxicity
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Asthma / chemically induced
  • Asthma / drug therapy*
  • Asthma / genetics
  • Asthma / pathology
  • Gene Expression Regulation
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Pneumonia / chemically induced
  • Pneumonia / drug therapy*
  • Pneumonia / genetics
  • Pneumonia / pathology
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Pulmonary Disease, Chronic Obstructive / chemically induced
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / genetics
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Edema / chemically induced
  • Pulmonary Edema / drug therapy*
  • Pulmonary Edema / genetics
  • Pulmonary Edema / pathology
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / genetics
  • Pulmonary Fibrosis / pathology
  • Signal Transduction
  • Transient Receptor Potential Channels / antagonists & inhibitors
  • Transient Receptor Potential Channels / genetics*
  • Transient Receptor Potential Channels / metabolism


  • Air Pollutants
  • Anti-Inflammatory Agents
  • Protein Isoforms
  • Transient Receptor Potential Channels