ovalbumin and capsazepine

To determine the immunologic functions of TRPA1 or TRPV1 in allergic conjunctivitis (AC).. Mice were sensitized with ovalbumin (OVA), after which TRPA1 antagonist or TRPV1 antagonist was administered before topical OVA challenge. Expression of TRPV1 or TRPA1 in AC was examined by western blotting and multicolor immunofluorescence. Clinical signs, OVA-specific IgE, infiltration of inflammatory cells into conjunctivae (CJs), and Th2 cytokine in draining lymph nodes (LNs) were evaluated by microscopy, flow cytometry, and ELISA.. TRPV1 expression was increased in CJs and LNs from AC mice, but TRPA1 expression was only increased in LNs. TRPV1 antagonist but not TRPA1 antagonist attenuated the clinical signs of AC and OVA-specific IgE in sera. TRPV1 antagonist furthermore inhibited the infiltration of inflammatory cells into CJ and the production of Th2 cytokines in LNs.. TRPV1 antagonist but not TRPA1 antagonist may ameliorate AC by suppressing the Th2 response in LNs.

Topics: Acetanilides; Animals; Blotting, Western; Capsaicin; Conjunctivitis, Allergic; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Eosinophils; Fluorescent Antibody Technique, Indirect; Immunoglobulin E; Male; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Purines; TRPA1 Cation Channel; TRPV Cation Channels

Asthma 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.. To 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/m(3)); (d) ovalbumin+formaldehyde (3.0 mg/m(3)); (e) ovalbumin+formaldehyde (3.0 mg/m(3))+HC-030031 (transient receptor potential ankyrin 1 antagonist); (f) ovalbumin+formaldehyde (3.0 mg/m(3))+ 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/m(3)) 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.. Formaldehyde 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.

Topics: Acetanilides; Animals; Asthma; Calcitonin Gene-Related Peptide; Capsaicin; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Formaldehyde; Immunoglobulin E; Immunohistochemistry; Interleukin-1beta; Interleukin-4; Interleukin-6; Lung; Male; Mice; Mice, Inbred BALB C; Neuropeptides; Ovalbumin; Purines; Substance P; Transient Receptor Potential Channels

Hyperplasia of airway smooth muscle cells (ASMC) is a major contributor to airway remodeling in asthma. Transient receptor potential vanilloid 1 (TRPV1) is an important channel to mediate Ca(2+) influx. This study explores the expression of TRPV1 channel and its effect on the proliferation and apoptosis in rat ASMC, in order to find a new target to treat airway remodeling in asthma.. Rats were sensitized and challenged with ovalbumin to replicate asthmatic models. Proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. Reverse transcriptase-polymerase chain reaction, immunocytochemistry, and Western blot were used to detect the mRNA and protein expression of TRPV1 channel. Intracellular calcium ([Ca(2+)]i) was detected using confocal fluorescence Ca(2+) imaging. [(3)H] thymidine incorporation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were used to observe the DNA synthesis and proliferation. TUNEL assay was used to detect the apoptosis of ASMC.. (1) The expression of PCNA was significantly increased in intact asthmatic rat ASMC. (2) The expression of TRPV1 channel was significantly increased in asthmatic rat ASMC. (3) [Ca(2+)]i in ASMC of the asthmatic group was significantly increased. After treatment with TRPV1 agonist capsaicin (CAP), [Ca(2+)]i was further increased, whereas [Ca(2+)]i was decreased after administration of TRPV1 antagonist capsazepine (CPZ) in ASMC of the asthmatic group. (4) The DNA synthesis and absorbance of MTT were significantly increased, while apoptosis was significantly decreased in asthmatic ASMC. CAP further enhanced proliferation and decreased apoptosis. CPZ significantly inhibited the effect of CAP in asthmatic ASMC.. TRPV1 channel was involved in the regulation of proliferation and apoptosis in asthmatic ASMC.

Topics: Airway Remodeling; Animals; Apoptosis; Asthma; Calcium; Capsaicin; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Hyperplasia; Male; Myocytes, Smooth Muscle; Ovalbumin; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley; Respiratory System; TRPV Cation Channels

To investigate the possible role of the vanilloid receptor-1 (TRPV1) in allergic airway responses, the effect of the specific TRPV1 receptor antagonist capsazepine was examined. Capsazepine significantly decreased the ovalbumin-induced contraction of isolated tracheal rings from ovalbumin-sensitized guinea pigs. This is the first report directly showing the involvement of the TRPV1 in experimental allergic airway responses.

Topics: Allergens; Animals; Capsaicin; Guinea Pigs; In Vitro Techniques; Male; Muscle Contraction; Ovalbumin; Receptors, Drug; Trachea