Inhibition of p21-activated kinase 1 attenuates the cardinal features of asthma through suppressing the lymph node homing of dendritic cells.

Inhibition of p21-activated kinase 1 attenuates the cardinal features of asthma through suppressing the lymph node homing of dendritic cells. Biochem Pharmacol. 2018 Jun 12;: Authors: Lu M, Xu C, Zhang Q, Wu X, Tang L, Wang X, Wu J, Wu X Abstract Dendritic cell (DC) trafficking from lung to the draining mediastinal lymph nodes (MLNs) is a key step for initiation of T cell responses in allergic asthma. In the present study, we investigate the role of DC-mediated airway inflammation after inhibition of p21-activated kinase-1 (PAK1), an effector of Rac and Cdc42 small GTPases, in the allergen-induced mouse models of asthma. Systemic administration of PAK1 specific inhibitor IPA-3 significantly attenuates not only the airway inflammation but also the airway hyperresponsiveness in a mouse model of ovalbumin-induced asthma. Specifically, intratracheal administration of low dosage of IPA-3 consistently decreases not only the airway inflammation but also the DC trafficking from lung to the MLNs. Importantly, intratracheal instillation of IPA-3-treated and ovalbumin-pulsed DCs behaves largely the same as that of either Rac inhibitor-treated and ovalbumin-pulsed DCs or Cdc42 inhibitor-treated and ovalbumin-pulsed DCs in attenuation of the airway inflammation in ovalbumin-challenged mice. Mechanistically, PAK1 is not involved in the maturation, apoptosis, antigen uptake, and T cell activation of cultured DCs, but PAK1 dose lie on the downstream...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research