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Nucleobindin 2 mediates eosinophilic airway inflammation in experimental house dust mite-induced asthma

Tuesday, October 25, 2011 — Poster Session II

Noon – 2:00 p.m.

Natcher Conference Center

NHLBI

CELLBIO-9

Authors

  • J Lam
  • X Yao
  • C Dai
  • K Fredriksson
  • M Yu
  • K Keeran
  • G Zywicke
  • D Malide
  • S Levine

Abstract

NUCB2 is a calcium-binding, EF-hand protein that binds ARTS-1 to regulate the release of soluble TNFR1 ectodomains and TNFR1 exosome-like vesicles. Here, we investigated the role of NUCB2 in the pathogenesis of house dust mite (HDM)-induced asthma. C57BL/6J wild-type (WT) mice and NUCB2 knockout mice (NUCB2-/-) received intranasal challenges with HDM (D. pteronyssinus, 25 μg) or saline five days a week for four weeks. Lungs were harvested for bronchoalveolar lavage fluid (BALF), inflammatory cells, protein and histopathology. Serum was also collected. First, we demonstrated that NUCB2 is expressed in the lung by CD68+ macrophages. Eosinophilic airway inflammation was also attenuated in HDM-challenged NUCB2-/- mice based on a reduction in the total number of cells, specifically eosinophils, in the BALF and a decrease in peri-bronchial cellular infiltrates on lung histopathology. Lung mRNA levels of Th2 cytokines, IL-5 and IL-13, were decreased in HDM-challenged NUCB2-/- mice. BALF protein levels of CCL24, Chi3L3/4, Chi3L-1, CCL17 and CCL22, which promote Th2 type responses, were also reduced. HDM-induced increases in serum IgE and goblet cell hyperplasia were not modified in HDM-challenged NUCB2-/- mice. NUCB2 promotes HDM-induced airway inflammation by regulating the release of chemotactic proteins that mediate the recruitment of eosinophils to the lung.

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