Cholinergic anti-inflammatory pathway confers airway protection against oxidative damage and attenuates inflammation in an allergic asthma model |
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| Authors: | Géssica Luana Antunes Josiane Silva Silveira Daniela Benvenutti Kaiber Carolina Luft Mariana Severo da Costa Eduardo Peil Marques Fernanda Silva Ferreira Ricardo Vaz Breda Angela T. S. Wyse Renato Tetelbom Stein Paulo Márcio Pitrez Aline Andrea da Cunha |
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| Affiliation: | 1. Laboratory of Pediatric Respirology, Infant Center, School of Medical, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Porto Alegre, Brazil;2. Laboratory of Neuroprotection and Metabolic Disease, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, Brazil;3. Laboratory of Neurosciences, Brain Institute - BraIns, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Porto Alegre, Brazil;4. Laboratory of Pediatric Respirology, Infant Center, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Hospital Moinhos de Vento, HMV, Porto Alegre, Brazil |
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| Abstract: | Asthma is characterized by the influx of inflammatory cells, especially of eosinophils as well as reactive oxygen species (ROS) production, driven by the release of the T helper 2 (Th2)-cell-associated cytokines. The cholinergic anti-inflammatory pathway (CAP) inhibit cytokines production and controls inflammation. Thus, we investigated the effects of pharmacological activation of CAP by neostigmine on oxidative stress and airway inflammation in an allergic asthma model. After the OVA challenge, mice were treated with neostigmine. We showed that CAP activation by neostigmine reduced the levels of pro-inflammatory cytokines (IL-4, IL-5, IL-13, IL-1β, and TNF-α), which resulted in a decrease of eosinophils influx. Furthermore, neostigmine also conferred airway protection against oxidative stress, attenuating ROS production through the increase of antioxidant defense, evidenced by the catalase (CAT) activity. We propose, for the first time, that pharmacological activation of the CAP can lead to new possibilities in the therapeutic management of allergic asthma. |
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| Keywords: | airway inflammation asthma cholinergic anti-inflammatory pathway neostigmine oxidative stress |
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