1. Academic Validation
  2. Rho-kinase inhibitor attenuates airway mucus hypersecretion and inflammation partly by downregulation of IL-13 and the JNK1/2-AP1 signaling pathway

Rho-kinase inhibitor attenuates airway mucus hypersecretion and inflammation partly by downregulation of IL-13 and the JNK1/2-AP1 signaling pathway

  • Biochem Biophys Res Commun. 2019 Aug 20;516(2):571-577. doi: 10.1016/j.bbrc.2019.06.072.
Wenqin Zhang 1 Xin Li 2 Yun Zhang 3
Affiliations

Affiliations

  • 1 Department of geriatric medicine, Tianjin Medical University General Hospital, Tianjin, 300052, China.
  • 2 Department of Respiratory Medicine, Tianjin Medical University General Hospital, Tianjin, 300073, China.
  • 3 Department of geriatric medicine, Tianjin Medical University General Hospital, Tianjin, 300052, China. Electronic address: [email protected].
Abstract

We measured the effect of Rho-kinase on inflammation and mucus hypersecretion in the airways of mouse models of asthma. Additionally, we aimed to determine if these effects were the result of JNK 1/2-AP1 pathway inhibition.We sensitized and challenged female C57BL/6 mice using house dust mites (HDM) followed by treatment with an inhibitor of Rho-kinase. Lung tissue was harvested to evaluate inflammation and mucus secretion in the airways of asthma mice. Cytokine expression in broncho-alveolar lavage fluid (BALF) was established by ELISA and airway responsiveness, and was determined by the invasive lung function test. JNK1/2, p-JNK1/2, AP-1, and p-AP-1 protein expression was determined by Western blot analysis. Asthma model mice that were treated with Rho-kinase inhibitor showed a significantly decrease in inflammation score, inflammatory cells, and airway responsiveness. Additionally, we found that IL-13 expressions in BALF and mucus secretion were decreased in HDM-challenged mice treated with Rho-kinase inhibitor. Furthermore, Rho-kinase inhibitor treatment decreased the expression of JNK1/2 and AP-1 phosphorylation. Our findings indicated that the Rho-kinase inhibitor decreased HDM-induced mucus secretion as well as airway inflammation in asthma mice through regulation of the JNK1/2-AP-1 pathway.

Keywords

Asthma; Interleukin-13; JNK mitogen; Rho-associated kinases.

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