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Pim1 kinase activity preserves airway epithelial integrity upon house dust mite exposure

Vries, de, M., Hesse, L., Jonker, M. R., van den Berge, M., van Oosterhout, A. J. M., Heijink, I. H. & Nawijn, M. C., 1-Dec-2015, In : American Journal of Physiology - Lung Cellular and Molecular Physiology. 309, 11, p. L1344-L1353 10 p.

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  • Pim1 kinase activity preserves airway epithelial integrity upon house

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DOI

Most patients with allergic asthma are sensitized to house dust mite (HDM). The allergenicity of HDM largely depends on disruption of the integrity and proinflammatory activation of the airway epithelium. In this study, we hypothesized that Pim1 kinase activity attenuates HDM-induced asthma by preserving airway epithelial integrity. The effects of Pim1 kinase activity on barrier function and release of the proinflammatory mediators IL-1 alpha and CCL20 were studied in vitro in 16HBE and primary bronchial epithelial cells (PBECs). Pim1-proficient and -deficient mice were exposed to a HDM-driven model of allergic asthma, and airway hyperresponsiveness (AHR) was measured upon methacholine challenge. Airway inflammation and proinflammatory mediators in lung tissue and BAL fluid were determined. We observed that inhibition of Pim1 kinase prolongs the HDM-induced loss of barrier function in 16HBE cells and sensitizes PBECs to HDM-induced barrier dysfunction. Additionally, inhibition of Pim1 kinase increased the HDM-induced proinflammatory activity of 16HBE cells as measured by IL-1 alpha secretion. In line herewith, HDM exposure induced an enhanced production of the proinflammatory chemokines CCL17 and CCL20 in Pim1-deficient mice compared with wild-type controls. While we observed a marked increase in eosinophilic and neutrophilic granulocytes as well as mucus cell metaplasia and AHR to methacholine in mice exposed to HDM, these parameters were independent of Pim1 kinase activity. In contrast, levels of the Th2-cytokines IL-5 and IL-10 were significantly augmented in HDM-treated Pim1-deficient mice. Taken together, our study shows that Pim1 kinase activity maintains airway epithelial integrity and protects against HDM-induced proinflammatory activation of the airway epithelium.

Original languageEnglish
Pages (from-to)L1344-L1353
Number of pages10
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume309
Issue number11
Publication statusPublished - 1-Dec-2015

    Keywords

  • Th2-cytokines, epithelial barrier function, allergen, innate immune response, eosinophils, INNATE LYMPHOID-CELLS, ALLERGIC SENSITIZATION, BARRIER DYSFUNCTION, E-CADHERIN, ASTHMA, INFLAMMATION, INHIBITION, CYTOKINES, RELEASE, DER-P-1
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