Inverse relationship between Sec14l3 mRNA/protein expression and allergic airway inflammation.
Bronchial asthma is an inflammatory disease of the airways. The Sec14l3 gene, encoding a 45-kDa secretory protein, is specifically expressed in airway epithelium. Here, we report on the kinetics of Sec14l3 expression following allergic inflammation of the lung. Brown Norway rats were sensitized by intraperitoneal injection of ovalbumin, followed by challenge with aerosolized ovalbumin after a 3-week interval. This animal model showed many features similar to human allergic asthma: an increase in inflammatory cells such as eosinophils, lymphocytes and neutrophils in bronchoalveolar lavage (BAL) fluid and histopathological alteration of lung tissue, exhibiting infiltration of these inflammatory cells and degeneration and necrosis of alveolar epithelium. These parameters reached their maximal level 24h after allergen challenge. In contrast, quantitative polymerase chain reaction analyses demonstrated a rapid and significant reduction of Sec14l3 mRNA in lung tissue and maximum reduction (to 1.4% of the control) was observed at 24h. Pretreatment with dexamethasone significantly suppressed both the Sec14I3 mRNA reduction and all of the inflammatory changes. The 45-kDa secretory protein was identified in the supernatant of BAL fluids. Two-dimensional gel images of the supernatant proteome also revealed down-regulation of the protein following inflammation (to approximately 30% of the control at 24h). Thus, Sec14l3 expression is highly and inversely associated with the progression of airway inflammation. Sec14l3 mRNA and protein may function in the homeostasis of airway epithelial cells under normal conditions.
Shan
Lihua
L
Bioscience Department, Tsukuba Research Laboratories, GlaxoSmithKline KK, Tsukuba, Japan. shanlihua2002@hotmail.com
Kawakami
Takao
T
Asano
Satoshi
S
Noritake
Shinobu
S
Yoshimoto
Daisuke
D
Yamashita
Keizo
K
Kikkawa
Hideo
H
Kinoshita
Mine
M
Matsubara
Shigeki
S
D000485:Allergens / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics*; D003907:Dexamethasone / Q000276:immunology / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D000485:Allergens; D002352:Carrier Proteins; D012333:RNA, Messenger; C544315:Sec14l3 protein, rat; D003907:Dexamethasone