1. Group III secreted phospholipase A2 transgenic mice spontaneously develop inflammation
- Author
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Kei Yamamoto, Makoto Murakami, Yuki Isogai, Hiroyasu Sato, Seiko Masuda, Tetsuyuki Kobayashi, and Yoshitaka Taketomi
- Subjects
HDC, histidine decarboxylase ,Chemokine ,LNL, LoxP–neomycin-resistance gene–LoxP ,MPO, myeloperoxidase ,Dermatitis ,Acanthosis ,Biochemistry ,PC, phosphatidylcholine ,Mice ,chemistry.chemical_compound ,LDL, low-density lipoprotein ,Prostaglandin E2 ,mPGES, microsomal prostaglandin E synthase ,Skin ,ESI, electrospray ionization ,RT, reverse transcription ,Group III Phospholipases A2 ,MCP-1, monocyte chemoattractant protein-1 ,GAPDH, glyceraldehyde-3-phosphate dehydrogenase ,TNFα, tumour necrosis factor α ,LPS, lipopolysaccharide ,prostaglandin ,medicine.symptom ,NK, natural killer ,Research Article ,medicine.drug ,Genetically modified mouse ,LTB4, leukotriene B4 ,HDL, high-density lipoprotein ,Prostaglandin ,Mice, Transgenic ,Inflammation ,CAG, chicken β-actin ,Biology ,Gene Expression Regulation, Enzymologic ,COX, cyclo-oxygenase ,PAS, periodic acid–Schiff ,sPLA2, secretory PLA2 ,Tg, transgenic ,PLA2G2A (etc.), sPLA2 group IIA (etc.) ,PGE2, prostaglandin E2 ,medicine ,Animals ,IFN, interferon ,cPLA2, cytosolic PLA2 ,mMCP, mouse mast cell protease ,PAF, platelet-activating factor ,Parakeratosis ,Molecular Biology ,phospholipid ,splenomegaly ,PLA2, phospholipase A2 ,Cell Biology ,BRAK, breast- and kidney-expressed chemokine ,medicine.disease ,WT, wild-type ,Sialadenitis ,IL, interleukin ,transgenic mouse ,chemistry ,Immunology ,biology.protein ,phospholipase A2 - Abstract
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.
- Published
- 2009