Presentation: The Role of PKR Pathway in Acute Exacerbation of Severe Bronchial Asthma ( World Allergy Congress)

Friday, 16 October 2015

Hall D1 Foyer (Floor 3) (Coex Convention Center)

So Ri Kim, MD, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Yong Chul Lee, MD, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Dong Im Kim, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Yang Keun Rhee, MD, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Heung Bum Lee, MD, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Seoung Ju Park, MD, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Yeong Hun Choe Choe, MD, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Seung Yong Park, MD, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Asthma exacerbations are an exaggerated lower airway response to an environmental exposure. Triggers of asthma exacerbation include virus infection, allergen, environmental pollutants, occupational sensitisers and irritants, and some medicine such as aspirin. It is well known that respiratory viral infection is the most common cuase for severe asthma exacerbation. The double-stranded RNA (dsRNA)-activated serine/threonine kinase R (PKR) is well characterized as an essential component of the innate antiviral response. Moreover, PKR activation is associated with IgE class switching and subsequent induction of IgE-mediated disorders such as allergy and asthma. Meanwhile, PKR phosphorylates e-IF2α, one of branches for unfoled protein response (UPR). Conversely, endoplasmic reticulum (ER) stress activates PKR which stimulates various inflammatory signaling pathways. However, to date, there is little information on its role the asthma exacerbation, especially acute exacerbation of steroid-resistant severe asthma. In this study, we investigated whether PKR activation is involved in the induction of asthma exacerbation using a mouse model of acute asthma exacerbation induced by the administration of poly (I:C). We found that the administration of poly (I:C) aggravated the all severe asthmatic features compared to those in mice sensitized with ovalbumin (OVA) and lipopolysaccharide (LPS) and challenged with OVA (OVA_LPS-OVA mice); the number of airway inflammatory cells in bronchioalveolar lavage (BAL) fluids, airway hyperresponsiveness, and the expression of Th2 cytokines, IL-17 and KC in lung tissues. Interestingly, the PKR expression was also more increased in lung tissues from OVA_LPS-OVA mice treated with poly (I:C) than OVA_LPS-OVA mice. Moreover, the phosphorylation of PKR in primary cultured tracheal epithelial cells was further enhanced in OVA_LPS-OVA mice treated with poly (I:C). This study indicates that PKR activation plays an important role the induction of acute exacerbation of severe neutrophilic asthma, highlighting the therapeutic potential of PKR inhibitor as a potent controller of acute asthma exacerbation in severe asthmatic patients.

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