Human TRPV1 and TRPA1 are receptors for bacterial quorum sensing molecules

Abstract

In this study, we investigated the activation of TRPV1 and TRPA1 by N-acyl homoserine lactones, quorum sensing molecules produced by Gram-negative bacteria, and the inhibitory effect of TRPV1 and TRPA1 by autoinducing peptides (AIPs), quorum sensing molecules produced by Gram-positive bacteria, using human embryonic kidney 293T cell lines stably expressing human TRPV1 and TRPA1, respectively. As a result, we found that some N-acyl homoserine lactones, such as N-octanoyl-L-homoserine lactone (C8-HSL), N-nonanoyl-L-homoserine lactone (C9-HSL) and N-decanoyl-L-homoserine lactone (C10-HSL), activated both TRPV1 and TRPA1. In addition, we clarified that some N-acyl homoserine lactones, such as N-3-oxo-dodecanoyl-L-homoserine lactone (3-oxo-C12-HSL), only activated TRPV1 and N-acyl homoserine lactones having saturated short acyl chain, such as N-acetyl-L-homoserine lactone (C2-HSL) and N-butyryl-L-homoserine lactone (C4-HSL), only activated TRPA1. Furthermore, we found that an AIP, simple linear peptide CHWPR, inhibited both TRPV1 and TRPA1 and peptide having thiolactone ring DICNAYF, the thiolactone ring were formed between C3 to F7, strongly inhibited only the TRPV1. Although the specificity of TRPV1 and TRPA1 for quorum sensing molecules was different, these data suggest that both TRPV1 and TRPA1 would function as receptors for quorum sensing molecule produced by bacteria. Graphical Abstract.

Keywords: Abbreviations:AHL; N-acyl homoserine lactone; AhR; aryl hydrocarbon receptor; AIP; autoinducing peptide; HSL; homoserine lactone; IL; interleukin; [Ca2+]i; intracellular Ca2+ concentration; IQGAP1; IQ-motif-containing GTPase-activating protein; LPS; lipopolysaccharide; PPAR; peroxisome proliferator activated receptor; T2R; taste receptor type 2; TRPA1; transient receptor potential cation channel; subfamily A; member 1; TRPM3; transient receptor potential cation channel; subfamily M; member 3; TRPM8; transient receptor potential cation channel; subfamily M; member 8; TRPV1; transient receptor potential cation channel; subfamily V; member 1; TRPV2; transient receptor potential cation channel; subfamily V; member 2; TRPV4; transient receptor potential cation channel; subfamily V; member 4; C2-HSL; N-acetyl-L-homoserine lactone; C4-HSL; N-butyryl-L-homoserine lactone; C6-HSL; N-hexanoyl-L-homoserine lactone; C7-HSL; N-heptanoyl-L-homoserine lactone; C8-HSL; N-octanoyl-L-homoserine lactone; C9-HSL; N-nonanoyl-L-homoserine lactone; C10-HSL; N-decanoyl-L-homoserine lactone; C11-HSL; N-undecanoyl-L-homoserine lactone; C12-HSL; N-dodecanoyl-L-homoserine lactone; C13-HSL; N-tridecanoyl-L-homoserine lactone; C14-HSL; N-tetradecanoyl-L-homoserine lactone; C15-HSL; N-pentadecanoyl-L-homoserine lactone; C16-HSL; N-hexadecanoyl-L-Homoserine lactone; 3-oxo-C6-HSL; N-(β-ketocaproyl)-L-homoserine lactone; 3-oxo-C8-HSL; N-3-oxo-octanoyl-L-homoserine lactone; 3-oxo-C10-HSL; N-3-oxo-decanoyl-L-homoserine lactone; 3-oxo-C12-HSL; N-3-oxo-dodecanoyl-L-homoserine lactone; 3-oxo-C14-HSL; N-3-oxo-tetradecanoyl-L-homoserine lactone; 3-oxo-C16-HSL; N-3-oxo-hexadecanoyl-L-homoserine lactone; OH-C8-HSL; N-3-hydroxyoctanoyl-L-homoserine lactone; OH-C10-HSL; N-3-hydroxydecanoyl-L-homoserine lactone; C14:1-Δ9-cis-HSL; N-cis-tetradec-9Z-enoyl-L-homoserine lactone; C16:1-Δ9-cis-HSL; N-cis-hexadec-9Z-enoyl-L-homoserine lactone; C18:1-Δ9-cis-HSL; N-cis-octadec-9Z-enoyl-L-homoserine lactone; 3-oxo-C14:1-Δ7-cis-HSL; N-3-oxo-tetradec-7(Z)-enoyl-L-homoserine lactone; 3-oxo-C16:1-Δ11-cis-HSL; N-3-oxo-hexadec-11(Z)-enoyl-L-homoserine lactone; N-acyl homoserine lactones; TRPA1; TRPV1; autoinducing peptides; quorum sensing molecules.