Cholinergic anti‐inflammatory pathway confers airway protection against oxidative damage and attenuates inflammation in an allergic asthma model

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.

Effects of VAChT reduction and α7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammation

“…Anti-cholinergic therapy has been suggested to intensify eosinophil interactions with airway nerves in a model of asthma in guinea pigs (Verbout et al, 2009). In according to this idea, Antunes et al ( 2019) (Antunes et al, 2019) recently showed that the pharmacological Fig. 10.…”

Dysfunction of the Autonomic Nervous System and Its Role in the Pathogenesis of Septic Critical Illness (Review)

“…A model of allergic asthma was used to study the neostigmine-induced activation of CAP and its effect on oxidative stress and airway inflammation. Activation of CAP with neostigmine reduced the levels of pro-inflammatory cytokines (IL-4, IL-5, IL-13, IL-1β, and TNF-α), which, in turn, reduced the inflow of eosinophils into the bronchial mucosa [ 52 ].…”

New Pathways for the Skin's Stress Response: The Cholinergic Neuropeptide SLURP-1 Can Activate Mast Cells and Alter Cytokine Production in Mice

“…To our surprise, a screen of the respective literature revealed that the precise role of the CS in the response to psychosocial stress is largely unknown and even less is known about a role for SLURP-1. Some information was even contradictory, suggestive of both, a protective and a harmful role of the CS in host defense and inflammatory disease (12,16,(23)(24)(25). This called for research that clarifies the role of SLURP-1 at the crossroads between pro-inflammatory and anti-inflammatory stress responses.…”