Cloning of a gene for a novel epithelium-specific cytosolic phospholipase A2, cPLA2delta, induced in psoriatic skin.
Psoriasis is a common skin disease characterized by hyperplastic regenerative epidermal growth and infiltration of immunocytes. The etiology of psoriasis is unknown, although several genetic and cellular factors have been elucidated. To find new psoriasis-related genes, we have cloned cDNAs that are differentially expressed between normal and psoriatic skins. Among these clones, we have identified a new gene that codes for a new member of the type IV cytosolic phospholipase A(2) (cPLA(2)) family. We refer to this gene as cPLA(2)delta. It encodes a polypeptide of 818 amino acids that has significant homology with known cPLA(2) proteins in the C2 and catalytic domains. The cPLA(2)delta gene was mapped to the 15q13-14 chromosomal locus, near to the locus of the cPLA(2)beta gene, from which it is separated by a physical distance of about 220 kb. To identify the phospholipase A(2) activity of cPLA(2)delta, we transfected COS-7 cells with His-tagged cPLA(2)delta. The cell lysate from these cells had calcium-dependent phospholipase A(2) activity. Northern blot analysis revealed that a cPLA(2)delta transcript of about 4 kb is expressed in stratified squamous epithelia, such as those in skin and cervix, but not in other tissues. In situ hybridization and immunohistochemistry revealed that cPLA(2)delta is expressed strongly in the upper spinous layer of the psoriatic epidermis, expressed weakly and discontinuously in atopic dermatitis and mycosis fungoides, and not detected in the epidermis of normal skin; cPLA(2)alpha is not detected in either normal or psoriatic skin. These results suggest that cPLA(2)delta exhibits a unique distribution pattern compared with that of known cPLA(2) subtypes, and it may play a critical role in inflammation in psoriatic lesions.
Chiba
Hiroaki
H
Discovery and Pharmacology Research Laboratories, Tanabe Seiyaku Co. Ltd., 16-89 Kashima 3-chome, Yodogawa-ku, Osaka 532-8505, Japan.
Michibata
Hideo
H
Wakimoto
Koji
K
Seishima
Mariko
M
Kawasaki
Satoshi
S
Okubo
Kousaku
K
Mitsui
Hiroshi
H
Torii
Hideshi
H
Imai
Yuji
Y
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D020134:Catalytic Domain; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D003001:Cloning, Molecular; D003600:Cytosol / Q000201:enzymology*; D018076:DNA, Complementary / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000201:enzymology; D004817:Epidermis / Q000201:enzymology; D004848:Epithelium / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation / Q000378:metabolism; D008969:Molecular Sequence Data; D009182:Mycosis Fungoides / Q000201:enzymology; D010455:Peptides / Q000737:chemistry; D010741:Phospholipases A / Q000235:genetics*; D054467:Phospholipases A2; D011565:Psoriasis / Q000201:enzymology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection
D018076:DNA, Complementary; D010455:Peptides; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium