Glutamine preferentially inhibits T-helper type 2 cell-mediated airway inflammation and late airway hyperresponsiveness through the inhibition of cytosolic phospholipase A(2) activity in a murine asthma model.
BACKGROUND
The non-essential amino acid, l-glutamine (Gln), is abundant in the human body. Gln exhibits beneficial effects on endotoxic shock through the inhibition of cytosolic phospholipase A(2) (cPLA(2)) activity. cPLA(2) has been reported to be implicated in the pathogenesis of asthma, but the effects of Gln on asthma have not yet been defined.


OBJECTIVE
To investigate the effects of Gln on allergic bronchial inflammation and airway hyperresponsiveness (AHR), and to determine the possible action mechanisms of Gln in a murine model of asthma.


METHODS
cPLA(2) phosphorylation was assessed by immunoprecipitation and Western blotting. Smears of bronchoalveolar lavage cells were stained with Diff-Quik solution for differential cell counting. Airway levels of the proteins [T-helper type-1 (Th1) and Th2 cytokines, and mucin] were measured by ELISA. mRNA expression of cytokines was assessed by real-time RT-PCR. AHR was assessed as a change in airway resistance (RL). Histological studies were performed to assess the levels of mucin and pulmonary inflammation.


RESULTS
Systemic Gln administration inhibited cPLA(2) phosphorylation and its enzymatic activity in the lungs. Additionally, Gln effectively suppressed the key features of Th2-dependent asthmatic features, such as airway eosinophilia, mucus formation, and airway type 2 cytokine production, as well as late AHR.


CONCLUSIONS
Gln was found to be effective in the suppression of Th2-dependent phenotypes and late AHR, and this effect of Gln appeared to be at least partially attributable to its ability to suppress cLPA(2) activity in the airway. Our results suggest that clinical use of Gln for patients with asthma may be beneficial.
Ko
H M
HM
Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Gwangju, Republic of Korea.
Kang
N I
NI
Kim
Y S
YS
Lee
Y M
YM
Jin
Z W
ZW
Jung
Y J
YJ
Im
S Y
SY
Kim
J H
JH
Shin
Y H
YH
Cho
B H
BH
Lee
H K
HK
D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology; D001991:Bronchitis / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D005973:Glutamine / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D054510:Phospholipases A2, Cytosolic / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
D016207:Cytokines; D005973:Glutamine; D054510:Phospholipases A2, Cytosolic