Glutamine suppresses dinitrophenol fluorobenzene-induced allergic contact dermatitis and itching: inhibition of contact dermatitis by glutamine.
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) activities 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 activity. Regarding the molecular mechanism of Gln, we have recently shown that Gln effectively inhibits cPLA(2) phosphorylation and activity.


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. cPLA(2) phosphorylation and activity were analyzed using Western blotting and a cPLA(2) assay kit, respectively.


RESULTS
Topical application of Gln significantly attenuated inflammatory symptoms (ear thickness, histological inflammatory skin reactions) as well as itching. Gln inhibited cPLA(2) phosphorylation and enzymatic activity. Arachidonyl trifluoromethyl ketone (AACOCF(3)) inhibited cPLA(2) activity in DNFB-challenged ears and attenuated DNFB-induced ear inflammation and itching.


CONCLUSIONS
The results indicate that Gln suppresses DNFB-induced dermatitis and itching, at least in part, by inhibiting cPLA(2) activity.
Institute of Hepato-Biliary and Pancreatic Surgery, Taishan Medical University, Shandong Province, Taiwan, ROC.
Zhe Wu
ZW
Jin
Hae-Kyoung
HK
Kim
Chang-Hoon
CH
Lee
Sung-Won
SW
Jung
Sook-Jeong
SJ
Shin
Suhn-Young
SY
Im
Baik-Hwan
BH
Cho
Hern-Ku
HK
Lee
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003593:Cytoplasm / Q000201:enzymology; D017449:Dermatitis, Allergic Contact / Q000378:metabolism* / Q000628:therapy*; D004140:Dinitrophenols / Q000737:chemistry*; D004423:Ear; D005260:Female; D005464:Fluorobenzenes / Q000737:chemistry*; D005973:Glutamine / Q000737:chemistry* / Q000378:metabolism; D015151:Immunoblotting / Q000379:methods; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D054467:Phospholipases A2 / Q000378:metabolism; D010766:Phosphorylation; D011537:Pruritus; D034622:RNA Interference
D000893:Anti-Inflammatory Agents; D004140:Dinitrophenols; D005464:Fluorobenzenes; D005973:Glutamine; D054467:Phospholipases A2