TRP Channels as Cellular Targets of Particulate Matter

Abstract

Particulate matter (PM) is constituted by particles with sizes in the nanometer to micrometer scales. PM can be generated from natural sources such as sandstorms and wildfires, and from human activities, including combustion of fuels, manufacturing and construction or specially engineered for applications in biotechnology, food industry, cosmetics, electronics, etc. Due to their small size PM can penetrate biological tissues, interact with cellular components and induce noxious effects such as disruptions of the cytoskeleton and membranes and the generation of reactive oxygen species. Here, we provide an overview on the actions of PM on transient receptor potential (TRP) proteins, a superfamily of cation-permeable channels with crucial roles in cell signaling. Their expression in epithelial cells and sensory innervation and their high sensitivity to chemical, thermal and mechanical stimuli makes TRP channels prime targets in the major entry routes of noxious PM, which may result in respiratory, metabolic and cardiovascular disorders. On the other hand, the interactions between TRP channel and engineered nanoparticles may be used for targeted drug delivery. We emphasize in that much further research is required to fully characterize the mechanisms underlying PM-TRP channel interactions and their relevance for PM toxicology and biomedical applications.

Keywords: TRP channel; TRPA1; TRPM2; TRPM8; TRPV1; TRPV4; diesel; nanoparticle; particular matter; smoke.

Figure 1

Schematic of the structure of (A) TRPA1, (B) TRPV1, (C) TRPM8 and (D) TRPV4 and the representative sites involved in the activation by PM. Modified from [51] (with permission).

Figure 2

Amorphous silica nanoparticles inhibit the chemical activation of TRPV4. Acute response elicited in cultured human airway epithelial (16HBE) cells by different concentration of 10 nm amorphous silica nanoparticles (SiNPs) and the corresponding TRPV4 inhibition ((a): 0 μg/mL, (b): 10 μg/mL, (c): 100 μg/mL, (d): 1000 μg/mL). (e) The influx in Ca²⁺ upon SiNPs challenging is concentration-dependent. (f) The inhibition of TRPV4 activation by agonist in the presence of SiNPs is concentration-dependent. Reproduced with permission from [24].

Figure 3

Changes in interleukin 8 (IL-8) mRNA expression as an indicator of inflammation induced by DEP originating from a “black smoker” diesel truck, a diesel exhaust filter regeneration machine, an emission station and NIST SRM 2975. TRPA1 inhibitor HC-030031 reduces the inflammatory effect. The symbols * and # indicate significant induction relative to control and significant inhibition by HC-030031, respectively. Reproduced with permission from [98].

Figure 4

Graphical summary of the activation of TRPA1, TRPC4, TRPM2, TRPM8 and TRPV3 channels by C₆₀ fullerenes, cigarette smoke (CS), wood smoke (WS), diesel exhaust (DE), ultrafine ambient particles (UFP), coal fly ash (CFA), zinc NPs (ZnNP), lanthanide NPs (LnNP), silica NPs (SiNP) and DOX-coated gold nanorods (AuNP).

Figure 5

Graphical summary of the activation of TRPV1, TRPV2 and TRPV4 channels by titanium NPs (TiNP), carbon NPs (CNP), coal fly ash (CFA), silica NPs (SiNP), ultrafine ambient particles (UFP), cigarette smoke (CS), diesel exhaust (DE) and magnetic particles (mag NP).