Group III secreted phospholipase A2 transgenic mice spontaneously develop inflammation.
PLA2 (phospholipase A2) group III is an atypical sPLA2 (secretory PLA2) that is homologous with bee venom PLA2 rather than with other mammalian sPLA2s. In the present paper, we show that endogenous group III sPLA2 (PLA2G3) is expressed in mouse skin and that Tg (transgenic) mice overexpressing human PLA2G3 spontaneously develop skin inflammation. Pla2g3-Tg mice over 9 months of age frequently developed dermatitis with hyperkeratosis, acanthosis, parakeratosis, erosion, ulcer and sebaceous gland hyperplasia. The dermatitis was accompanied by infiltration of neutrophils and macrophages and by elevated levels of pro-inflammatory cytokines, chemokines and prostaglandin E2. In addition, Pla2g3-Tg mice had increased lymph aggregates and mucus in the airway, lymphocytic sialadenitis, hepatic extramedullary haemopoiesis, splenomegaly with increased populations of granulocytes and monocytes/macrophages, and increased serum IgG1. Collectively, these observations provide the first demonstration of spontaneous development of inflammation in mice with Tg overexpression of mammalian sPLA2.
Department of Biological Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-Ku, Tokyo 112-8610, Japan.
Hiroyasu
H
Sato
Yoshitaka
Y
Taketomi
Yuki
Y
Isogai
Seiko
S
Masuda
Tetsuyuki
T
Kobayashi
Kei
K
Yamamoto
Makoto
M
Murakami
D000818:Animals; D003872:Dermatitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D054520:Group III Phospholipases A2 / Q000235:genetics* / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D012867:Skin / Q000473:pathology
D054520:Group III Phospholipases A2; C484163:PLA2G3 protein, human; C541931:PLA2G3 protein, mouse