Transient Receptor Potential Ankyrin 1 Enhances Ovalbumin-Induced Acute Allergic Inflammation in Murine Models

Abstract

Background: Transient receptor potential ankyrin 1 (TRPA1) is an ion channel known to mediate nociception and neurogenic inflammation, and to be activated by reactive oxygen and nitrogen species (ROS and RNS) produced at the sites of inflammation. Because neurogenic inflammation as well as the release of ROS and RNS are typical features of early stages of allergic responses, we hypothesized that TRPA1 may be involved in triggering and/or amplifying allergic inflammation. Objective: This study aims at exploring the role of TRPA1 ion channel in acute ovalbumin-induced allergic inflammation in applicable murine models. Methods: The effects of pharmacological blockade and genetic deletion of TRPA1 in ovalbumin-induced allergic conjunctivitis and acute paw inflammation were studied in mice sensitized to ovalbumin. Results: Ovalbumin-induced allergic conjunctivitis was milder in TRPA1-deficient mice and alleviated in wild-type mice treated with the TRPA1 antagonist TCS 5861528. Subcutaneous challenge with ovalbumin caused a significant paw edema and interleukin (IL)-4 production in sensitized mice; these responses were attenuated in animals treated with the TRPA1 antagonist and in TRPA1-deficient mice. Interestingly, blockade of the major secondary effector of TRPA1, substance P, also resulted in attenuated ovalbumin-induced paw edema and IL-4 production. However, the splenocytes’ responses to ovalbumin were similar in cells from wild-type and TRPA1-deficient mice sensitized to ovalbumin. Conclusion: These results introduce a novel concept that TRPA1 mediates early events in allergic inflammation, but does not seem to affect allergic sensitization, and could therefore be a novel drug target to treat conditions associated with allergic inflammation.

An initial assessment of the involvement of transglutaminase2 in eosinophilic bronchitis using a disease model developed in C57BL/6 mice

“…It has also been reported that IL-13 up-regulates TRPV1 in the bronchial epithelial cells in the lung of asthmatic BALB/c mice 54 . However, treatment directed at TRPV1 significantly alleviated IL-4, IL-5, and IL-13 level in a chronic asthma murine model, while conversely TRPA1 promoted OVA-induced IL-4 production during acute allergic lung inflammation 55 , 56 . These findings will guide us in further identifying the relationship and mechanisms of TG2 interaction with TRPA1, TRPV1 and IL-6 & IL-4, IL-13 using TG2 null mice and in vitro cultured cell.…”

The glucocorticoid dexamethasone alleviates allergic inflammation through a mitogen‐activated protein kinase phosphatase‐1‐dependent mechanism in mice

“…Wild‐type and MKP‐1 deficient C57BL/6 mice 6 originating from the R. Bravo laboratory at Bristol‐Myers Squibb Pharmaceutical Research Institute (Princeton, NJ, USA) were used in the experimental model of allergy. Mice were cared under standard conditions and anaesthetized as previously described 7 . The study was performed in accordance with the EU directive on the protection of animals used for scientific purposes (Directive 2010/63/EU) and upon approval of National Animal Experiment Board.…”

“…Mice were cared under standard conditions and anaesthetized as previously described. 7 The study was performed in accordance with the EU directive on the protection of animals used for scientific purposes (Directive 2010/63/ EU) and upon approval of National Animal Experiment Board. The animal experiments were conducted in the preclinical facility of Tampere University, Tampere, Finland, and the laboratory analyses were performed in the laboratory of the Immunopharmacology Research Group, Tampere University, Tampere, Finland, in 2021.…”

“…Ovalbumin-induced allergic paw edema model was carried out as previously described. 7 In short, mice were sensitized to ovalbumin with an i.p. injection on day 1, boosted with another i.p.…”