Potential Role of Transient Receptor Potential Vanilloid 1 and Ankyrin 1 in Colonic Inflammation in Dextran Sulfate Sodium (DSS)‐induced Murine Colitis
Authors: Utsumi Daichi , Matsumoto Kenjiro , Tsukahara Takuya , Amagase Kikuko , Tominaga Makoto , Kato Shinichi 
Published: November 2023

Background & AimTemperature‐activated transient receptor potential (TRP) channels, which are non‐selective cation channels, have important roles in the sensation of pain. Transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) are known to be activated by heat (>43°C) and cold (<17°C) stimulations, respectively, and control neurogenic inflammation. TRPV1 is reportedly co‐expressed with TRPA1 in sensory afferent neurons, suggesting the synergistic actions of TRPV1 and TRPA1 in regulating physiological and pathophysiological functions. Several studies showed that TRPV1 and TRPA1 promotes colonic inflammation via substance P release from sensory afferent neurons. In contrast, several studies demonstrated that some TRP channels are expressed in immune and inflammatory cells, and regulate immune and inflammatory responses in these cells. Thus, the regulatory roles of these channels in colonic inflammation have not yet been fully elucidated. In the present study, we investigated the potential roles of TRPV1 and TRPA1 in colonic inflammation in DSS‐induced murine colitis.MethodsTRPA1‐ and TRPV1KO and WT mice were used. Bone marrow chimeric mice were produced by implantation of bone marrow cells isolated from WT and either TRPV1‐ or TRPA1KO mice (donors) to WT and either TRPV1‐ or TRPA1KO mice (recipients) that received lethal dose of irradiation. Colitis was induced by administering 2% dextran sulfate sodium (DSS) in drinking water for 7 days. The disease activity index (DAI), colon length, myeloperoxidase (MPO) activity, and inflammatory cytokine expressions were examined. Further, the number of substance P (SP)‐ and calcitonin gene‐related peptide (CGRP)‐positive neurons in colonic mucosa was determined immunohistochemically.ResultsDSS treatment caused severe colitis accompanied by increases in DAI and MPO activity in WT mice but these responses were significantly attenuated in TRPV1KO and TRPA1KO mice. DSS‐induced upregulation of inflammatory cytokines was also significantly less in TRPV1KO and TRPA1KO mice than WT mice. Similar attenuations of colonic inflammation were observed in TRPV1KO mice transplanted with bone marrow cells isolated from WT or TRPV1KO mice and TRPA1KO mice transplanted with bone marrow cells isolated from WT or TRPA1KO mice but not in WT mice transplanted with bone marrow cells isolated from WT, TRPV1KO or TRPA1KO mice. DSS‐treatment increased the number of both SP‐ and CGRP‐positive neurons in the colon. The increase in SP‐positive neurons was significantly diminished whereas the increase in CGRP‐positive neurons was not affected in TRPV1KO and TRPA1KO mice.ConclusionThese results suggest that both TRPV1 and TRPA1 play a pathogenic role in colonic inflammation. TRPV1 and TRPA1 expressed in sensory neurons contribute to the progression of colonic inflammation via increase in SP release from sensory neurons.