Dexamethasone alters bronchoalveolar lavage fluid proteome in a mouse asthma model.
BACKGROUND
Glucocorticoid is the most effective anti-inflammatory agent for asthma. The spectrum of protein targets that can be regulated by glucocorticoid in asthma is not fully understood. The present study tried to identify novel protein targets of dexamethasone in allergic airway inflammation by analyzing the proteome of mouse bronchoalveolar lavage (BAL) fluid.


METHODS
BALB/c mice sensitized and challenged with ovalbumin (OVA) showed increased pulmonary inflammatory cell infiltration, airway mucus production and serum OVA-specific IgE level. Dexamethasone inhibited all these allergic airway inflammation endpoints. BAL fluid proteins were resolved by two-dimensional gel electrophoresis and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.


RESULTS
The levels of 26 BAL fluid proteins were found to be markedly altered by dexamethasone. A family of chitinases (Ym1, Ym2 and acidic mammalian chitinase, AMCase), lungkine, gob-5, surfactant protein D and polymeric immunoglobulin receptor have been found for the first time to be downregulated by dexamethasone in allergic airways. The downregulatory effects were confirmed by immunoblotting and RT-PCR analyses. Dexamethasone was also shown to significantly inhibit lavage fluid chitinase bioactivity. In addition, dexamethasone promoted airway expression of vitamin D-binding protein, heptoglobin and alpha(1)-antitrypsin.


CONCLUSIONS
Among all these newly identified protein targets of dexamethasone, AMCase and gob-5 have been shown to be pro-inflammatory in asthma. Downregulation of AMCase and gob-5 may be considered as two novel anti-inflammatory actions of glucocorticoid in asthma.
Zhao
Jing
J
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Yeong
Lai Han
LH
Wong
W S Fred
WS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000276:immunology; D002688:Chitinases / Q000096:biosynthesis / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D015180:Electrophoresis, Gel, Two-Dimensional; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009088:Mucoproteins / Q000096:biosynthesis / Q000187:drug effects; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy; D020543:Proteome / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000893:Anti-Inflammatory Agents; D009088:Mucoproteins; D020543:Proteome; D003907:Dexamethasone; D010047:Ovalbumin; C499254:CHIA protein, human; D002688:Chitinases