Aberrant expression of apoptosis-related molecules in psoriatic epidermis.
Apoptosis is a physiological form of cell death that is responsible for the deletion of cells. Epidermal keratinocytes are supposed to be regulated by cell proliferation and cell death leading to structural homeostasis. Psoriatic skin shows marked thickening of the epidermis, suggesting the imbalance of the homeostasis, which might be related to abnormal apoptotic process. We investigated the expression of various apoptosis-related molecules in the psoriatic hyperproliferative epidermis. Real time quantitative RT-PCR analyses revealed that mRNAs of Fas, Bcl-xL, Bax and ICAD (inhibitor of caspase 3-related DNase) of the psoriatic involved epidermis were increased by 4.2-, 2.8-, 2.6- and 5.6-fold, respectively, compared with the uninvolved epidermis. In contrast, Bcl-2 expression in the involved epidermis was one-third suppressed compared with the uninvolved epidermis. No significant difference in the expression of mRNAs of Fas ligand or CAD (caspase 3-related DNase) was detected between the involved and uninvolved epidermis. Western blot analysis and immunohistochemical studies showed compatible results obtained by RT-PCR analyses. Although active caspase 3 was slightly increased in the involved epidermis, apoptotic cells were marginally detected. These results indicate that psoriatic epidermis shows aberrant expression of apoptosis-related molecules representing suppressed apoptotic process, which might be related to characteristic histopathology.
Takahashi
Hidetoshi
H
Department of Dermatology, Asahikawa Medical College, 2-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido 078-8510, Japan. ht@asahikawa-med.ac.jp
Manabe
Akira
A
Ishida-Yamamoto
Akemi
A
Hashimoto
Yoshio
Y
Iizuka
Hajime
H
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002478:Cells, Cultured; D003199:Computer Systems; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015603:Keratinocytes / Q000473:pathology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling