title: Blockade of ankyrin repeat-rich membrane spanning protein modulates extracellular signal-regulated kinase expression and inhibits allergic inflammation in ovalbumin-sensitized mice.
abstract: Ankyrin repeat-rich membrane spanning protein (ARMS), also known as kinase D-interacting substrate of 220 kDa (Kidins220), is a transmembrane protein that has been reported to be involved in the pathogenesis of asthma through the nerve growth factor (NGF)/tyrosine kinase A (TrkA) receptor signaling pathway. To investigate whether NGF/TrkA-Kidins220/ARMS-extracellular signal-regulated kinase (ERK) signaling is activated in airway inflammation of asthma, BALB/c mice were sensitized and challenged with ovalbumin (OVA). The effects of Kidins220/ARMS on ERK, interleukin (IL)-1β, IL-4 and tumor necrosis factor (TNF)-α in lung tissues following the allergic airway challenge in mice were assessed by administering anti-ARMS antibody to the mice. Pathological changes in the bronchi and lung tissues were examined via hematoxylin and eosin staining. The phosphorylated ERK, IL-1β, IL-4 and TNF-α levels were determined using western blot analysis and ELISA and were found to be overexpressed in lung tissues following the allergen challenge. Moreover, after the mice were treated with anti-NGF, anti-TrkA or anti-ARMS, the levels of Kidins220/ARMS, phosphorylated ERK, IL-1β, IL-4, TNF-α and allergen-induced airway inflammation were downregulated. These results suggested that NGF/TrkA-Kidins220/ARMS-ERK signaling was activated in airway inflammation induced by the allergic airway challenge, possibly representing a new mechanism in asthma.
authors.affiliation: Department of Anatomy, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319, P.R. China ; Biopharmaceutical Institute, Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Ni
authors.affiliation: Department of Nephrology, Daqing People's Hospital, Daqing, Heilongjiang 163310, P.R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: Biopharmaceutical Institute, Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Tao
authors.affiliation: Biopharmaceutical Institute, Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Xu
authors.affiliation: Biopharmaceutical Institute, Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Ma
authors.affiliation: Biopharmaceutical Institute, Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wang
keywords: ankyrin repeat-rich membrane spanning protein; asthma; extracellular signal-regulated kinase; kinase D-interacting substrate of 220 kDa