Background
Cytoplasmic
phospholipase A
2 (
cPLA
2) is importantly implicated in a variety of inflammatory diseases by liberating arachidonic acid from phospholipids. The increased cPLA
2 act
ivities as well as increased levels of cPLA
2 metabolites are associated with pathogenesis of many inflammatory skin disorders including atopic dermatitis. The non-essential amino acid l-glutamine (Gln) has been reported to have an anti-inflammatory act
ivity. Regarding the molecular mechanism of Gln, we have recently shown that Gln effect
ively inhibits cPLA
2 phosphorylation and act
ivity.
Objective
To examine whether Gln could suppress allergic contact dermatitis (CD) induced on mouse ears by dinitrophenol fluorobenzene (DNFB).
Methods
Mice were sensitized five times on their ears with a 0.15 % solution of DNFB in a 3 day interval. To examine Gln effects, Gln solution (4 % in saline) was applied three times a day onto both sides of DNFB-applied ears from the last day of DNFB application. The inflammatory reactions of ears were evaluated by measuring ear thickness and hematoxylin and eosin (H&E) staining. Mouse scratching behavior was objectively evaluated using a MicroAct apparatus. cPLA2 phosphorylation and activity were analyzed using Western blotting and a cPLA2 assay kit, respectively.
Results
Topical application of Gln significantly attenuated inflammatory symptoms (ear thickness, histological inflammatory skin reactions) as well as itching. Gln inhibited cPLA2 phosphorylation and enzymatic activity. Arachidonyl trifluoromethyl ketone (AACOCF3) inhibited cPLA2 activity in DNFB-challenged ears and attenuated DNFB-induced ear inflammation and itching.
Conclusion
The results indicate that Gln suppresses DNFB-induced dermatitis and itching, at least in part, by inhibiting cPLA2 activity.
