Abnormal Bcl-2 and "tissue" transglutaminase expression in psoriatic skin.
Cell death by apoptosis plays a key role in skin development and homeostasis. Previous studies have shown that increased apoptosis characterizes several pathologic conditions affecting human skin. Thus, the pathogenesis of cutaneous diseases may involve an imbalance in the homeostatic mechanisms determining whether the death of keratinocytes will occur by terminal differentiation or apoptosis. We investigated the involvement of apoptosis in psoriasis. For this purpose, we assessed, in addition to morphology and DNA fragmentation, the expression of two putative apoptotic genes, bcl-2 and "tissue" transglutaminase, in normal and psoriatic skin. A large number of keratinocytes showing biochemical and morphologic features of cells undergoing apoptosis was observed in all the suprabasal layers of the psoriatic epidermis. The plaques from all patients analyzed showed a dramatic reduction in the number of bcl-2-positive cells localized in the basal cell compartment. In contrast, the psoriatic lesions presented a marked induction in "tissue" transglutaminase, which was localized specifically to the cytoplasm of apoptotic keratinocytes. "Tissue" transglutaminase protein staining was undetectable in normal epidermis. The bcl-2 and "tissue" transglutaminase staining pattern observed in psoriasis also was found in the skin of patients affected by lichen planus. These findings indicate that these two genes are regulated in an opposite fashion in psoriatic keratinocytes undergoing apoptosis, thus confirming their antithetic role in the cascade of events leading to the establishment of the mature apoptotic phenotype.
Bianchi
L
L
Department of Internal Medicine, University of Rome Tor Vergata, Italy.
Farrace
M G
MG
Nini
G
G
Piacentini
M
M
D017209:Apoptosis; D002455:Cell Division; D015536:Down-Regulation; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D011565:Psoriasis / Q000201:enzymology* / Q000235:genetics; D012867:Skin / Q000737:chemistry / Q000201:enzymology / Q000473:pathology*; D011503:Transglutaminases / Q000502:physiology*
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011503:Transglutaminases