Role of Transient Receptor Potential Ion Channels and Evoked Levels of Neuropeptides in a Formaldehyde-Induced Model of Asthma in Balb/c Mice

Abstract

ObjectiveAsthma is a complex pulmonary inflammatory disease characterized by the hyper-responsiveness, remodeling and inflammation of airways. Formaldehyde is a common indoor air pollutant that can cause asthma in people experiencing long-term exposure. The irritant effect and adjuvant effect are the two possible pathways of formaldehyde promoted asthma.Methodology/Principal FindingsTo explore the neural mechanisms and adjuvant effect of formaldehyde, 48 Balb/c mice in six experimental groups were exposed to (a) vehicle control; (b) ovalbumin; (c) formaldehyde (3.0 mg/m3); (d) ovalbumin+formaldehyde (3.0 mg/m3); (e) ovalbumin+formaldehyde (3.0 mg/m3)+HC-030031 (transient receptor potential ankyrin 1 antagonist); (f) ovalbumin+formaldehyde (3.0 mg/m3)+ capsazepine (transient receptor potential vanilloid 1 antagonist). Experiments were conducted after 4 weeks of combined exposure and 1-week challenge with aerosolized ovalbumin. Airway hyper-responsiveness, pulmonary tissue damage, eosinophil infiltration, and increased levels of interleukin-4, interleukin-6, interleukin-1β, immunoglobulin E, substance P and calcitonin gene-related peptide in lung tissues were found in the ovalbumin+formaldehyde (3.0 mg/m3) group compared with the values seen in ovalbumin -only immunized mice. Except for interleukin-1β levels, other changes in the levels of biomarker could be inhibited by HC-030031 and capsazepine.Conclusions/SignificanceFormaldehyde might be a key risk factor for the rise in asthma cases. Transient receptor potential ion channels and neuropeptides have important roles in formaldehyde promoted-asthma.

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

“…TRPA1 did not seem to affect the process of allergic sensitization, but we found a clear inhibitory effect of blockade of TRPA1 on the early vascular events and eosinophil accumulation in allergic reactions. As there is also previous evidence on the role of TRPA1 in ovalbumin-induced airway inflammation [15, 16], it is highly possible that the inhibition of TRPA1 will turn out to be an effective means to treat allergic conditions.…”

“…Previously, the role of TRPA1 in enhancing allergic inflammation was demonstrated in studies conducted in models of ovalbumin-induced experimental murine asthma [15, 16], IL-13-induced itch [39], and oxazolone-induced allergic contact dermatitis [11]. Interestingly, a previously known powerful contact sensitizer, 2,4-dinitrochlorobenzene, has also proven to be a direct activator of TRPA1 [40].…”

“…However, the previous studies focusing on the airway inflammation induced by ovalbumin, or ovalbumin and formaldehyde challenge, analyzed the outcome of a repeated/continuous exposure to the allergen lasting from several days to weeks [15, 16]. Interestingly, the results presented clear evidence that pharmacological blockade and genetic deletion of TRPA1 results in diminished amounts of proinflammatory cytokines and leukocytes in the bronchoalveolar lavage fluid, in addition to reduced airway hyperresponsiveness [15, 16]. TRPA1 expression has also been noted to increase as a result of ovalbumin-induced airway inflammation [41].…”

“…TRPA1 expression has also been noted to increase as a result of ovalbumin-induced airway inflammation [41]. The sensitization against ovalbumin was similar in the TRPA1-deficient and the wild-type mice, as measured by the ovalbumin-specific IgE in the serum, but the amounts of proinflammatory neuropeptides substance P, calcitonin gene-related peptide, and neurokinin A were reduced in the inflamed airways in TRPA1-deficient animals [15, 16]. Our study expands on the previous data on the role and mechanisms of TRPA1 in allergic conjunctivitis and acute allergic s.c. inflammation.…”

“…Activation of TRPA1 by exogenous or endogenous proinflammatory substances can induce acute inflammation [4] in conditions such as experimental paw inflammation [6], dermatitis [11], colitis [12], gout [13, 14], or osteoarthritis [10]. Interestingly, activation of TRPA1 was found to mediate also the development of airway inflammation in experimental asthma in mice following a repeated allergen challenge [15, 16]. Considering that neurogenic inflammation as well as the release of ROS and RNS are characteristics of the early stages of allergic inflammation [17], and that TRPA1 is linked to both these features, we hypothesized that TRPA1 may be a general mechanism involved in triggering and/or amplifying allergic inflammation.…”