Processing of cathepsins L, B and D in psoriatic epidermis.
Proteinase activity is increased in psoriatic epidermis. To elucidate the involvement of enzymes in psoriatic epidermis, the expression of cathepsins, L, B and D was investigated by Western blotting and immunohistological studies. Normal epidermis contained abundant inactive precursors (39 kDa) of cathepsins L and B and an inactive intermediate form (45 kDa) of cathepsin D. Cathepsin L in psoriasis was processed to a variable extent from the precursor to a single-chain form (30 kDa) and a mixture of single- and heavy-chain (25 kDa) forms of the active mature enzyme, corresponding to the immunohistological staining patterns 'diffuse dense', 'small granular', and unevenly distributed 'condensed granular'. Cathepsin B showed a mixture of precursor form (39 kDa) and single-chain (30 kDa) forms and was expressed as a 'diffuse dense' staining pattern in the mid-spinous layer and as a 'condensed' pattern in the upper spinous and granular layers. Cathepsin D was processed to the heavy-chain (31 kDa) form of activated mature enzyme with small granular staining and a mixture of heavy-chain and degraded protein (28 kDa) with larger and more condensed granular staining. The distribution patterns of 'small granular' cathepsin L, and of cathepsins B and D expression in suprabasal keratinocytes were very similar to that of involucrin. After complete clinical resolution of psoriasis by 8-methoxypsoralen plus UVA treatment, the expression of the three cathepsins was normalized. These results suggest that cathepsins L, B and D in forms activated to a variable extent may be involved in the pathology of psoriasis.
Kawada
A
A
Department of Dermatology, National Defense Medical College, Saitama, Japan.
Hara
K
K
Kominami
E
E
Hiruma
M
M
Noguchi
H
H
Ishibashi
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002401:Cathepsin B / Q000032:analysis*; D002402:Cathepsin D / Q000032:analysis*; D056668:Cathepsin L; D002403:Cathepsins / Q000032:analysis*; D002648:Child; D003546:Cysteine Endopeptidases / Q000032:analysis*; D010450:Endopeptidases; D004792:Enzyme Precursors / Q000032:analysis*; D004817:Epidermis; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis; D008875:Middle Aged; D011701:PUVA Therapy; D011498:Protein Precursors / Q000032:analysis; D011565:Psoriasis / Q000188:drug therapy / Q000201:enzymology*
D004792:Enzyme Precursors; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D011498:Protein Precursors; C032253:involucrin; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; D002402:Cathepsin D