The anti-asthmatic potential of Rho-kinase inhibitor hydroxyfasudil in the model of experimentally induced allergic airway inflammation

Fraňová, Soňa; Molitorisová, Milica; Kalmanova, Lenka; Palencarova, Jarmila; Jošková, Marta; Smieško, Lukáš; Mažerik, Jozef; Šutovská, Martina

doi:10.1016/j.ejphar.2022.175450

Cited by 6 publications

(2 citation statements)

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“…In ovalbumin-sensitized guinea pigs, ROCK inhibitor reversed histamine-and PGF2alpha-induced airway hyperresponsiveness [50]. Also, in a guinea pig model of ovalbumin-induced chronic allergic airway inflammation, specific airway resistance has been shown to be reduced, in concomitance with the reduction of multiple markers of inflammation and remodeling, by ROCK inhibition [51]. Other studies show the involvement of ROCK in inflammatory pathways linked to airway hyperresponsiveness.…”

Section: Overactive Rock Signaling In Asthmamentioning

confidence: 94%

“…Interleukin-17A, a cytokine released by T helper 17 cells, can increase bronchoconstriction induced by methacholine or KCL through RhoA/ROCK2 signaling [52], a finding consistent with ROCK inhibition of MLCP and thus enhanced ASM contractility. In rodent models of asthma, inhibition of ROCK suppresses pulmonary eosinophilia and the release of chemokines and cytokines [53][54][55], extracellular matrix remodeling [49], as well as airway inflammation [51,56,57]. Recently, interleukin-27 has been shown to down-regulate Rho/ROCK and reduce airway inflammation in a mouse model of asthma [58].…”

Section: Overactive Rock Signaling In Asthmamentioning

confidence: 99%

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Rho-Kinase Inhibition of Active Force and Passive Tension in Airway Smooth Muscle: A Strategy for Treating Airway Hyperresponsiveness in Asthma

Yasuda,

Wang,

Chitano

et al. 2024

Biology

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Rho-kinase inhibitors have been identified as a class of potential drugs for treating asthma because of their ability to reduce airway inflammation and active force in airway smooth muscle (ASM). Past research has revealed that, besides the effect on the ASM’s force generation, rho-kinase (ROCK) also regulates actin filament formation and filament network architecture and integrity, thus affecting ASM’s cytoskeletal stiffness. The present review is not a comprehensive examination of the roles played by ROCK in regulating ASM function but is specifically focused on passive tension, which is partially determined by the cytoskeletal stiffness of ASM. Understanding the molecular basis for maintaining active force and passive tension in ASM by ROCK will allow us to determine the suitability of ROCK inhibitors and its downstream enzymes as a class of drugs in treating airway hyperresponsiveness seen in asthma. Because clinical trials using ROCK inhibitors in the treatment of asthma have yet to be conducted, the present review focuses on the in vitro effects of ROCK inhibitors on ASM’s mechanical properties which include active force generation, relaxation, and passive stiffness. The review provides justification for future clinical trials in the treatment of asthma using ROCK inhibitors alone and in combination with other pharmacological and mechanical interventions.

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Section: Overactive Rock Signaling In Asthmamentioning

confidence: 94%