Alteration of the expression of Bcl-2, Bcl-x,Bax, Fas,and Fas ligand in the involved skin of psoriasis vulgaris following topical anthralin therapy

Anthralin (dithranol) is frequently used for the treatment of psoriasis. However, the mode of action of anthralin has not been completely elucidated as yet. Recent findings suggest that psoriatic keratinocytes are resistant to the apoptotic process. In this study, we examined the immunohistochemical expression of apoptosis-regulated protein in the involved psoriatic skin following topical anthralin therapy. Biopsy specimens were obtained from back skins treated with topical anthralin or white petrolatum (control) in 4 patients with psoriasis vulgaris. Immunohistochemical examination revealed that psoriatic keratinocytes expressed high levels of Bcl-x, which was significantly reduced after anthralin treatment. Bax was not detected in the epidermal keratinocytes in the petrolatum-treated skin, while it was present in the upper keratinocytes after anthralin therapy. Bcl-2 was detected only in basal layers of psoriatic epidermis following both petrolatum and anthralin application. Psoriatic keratinocytes expressed higher levels of Fas in the lower epidermis, while only weak expression was detected in anthralin-treated plaques. On the other hand, hyperproliferative keratinocytes strongly expressed Fas ligand (FasL) on their plasma membranes as well as infiltrating lymphocytes in the upper dermis. Furthermore, anthralin-treated psoriatic epidermis did not express FasL. In normal skin, keratinocytes expressed low to absent levels of Bcl-x and Bax, while Bcl-2 was detected only in melanocytes in basal layers. Neither Fas nor FasL were detected in the epidermis of normal skin. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining revealed positive labeling on the majority of psoriatic keratinocytes through the epidermis in petrolatum-treated skin, whereas anthralin treatment markedly reduced TUNEL-positive keratinocytes. These in vivo results may reflect improvement of the psoriatic skin following effective anthralin therapy.     

Abnormal aquaporin-3 protein expression in hyperproliferative skin disorders

Non-melanoma skin cancers (NMSCs) and psoriasis represent common hyperproliferative skin disorders, with approximately one million new NMSC diagnoses each year in the United States alone and a psoriasis prevalence of about 2% worldwide. We recently demonstrated that the glycerol channel, aquaporin-3 (AQP3) and the enzyme phospholipase D2 (PLD2) interact functionally in epidermal keratinocytes of the skin to inhibit their proliferation. However, others have suggested that AQP3 is pro-proliferative in keratinocytes and is upregulated in the NMSC, squamous cell carcinoma (SCC). To evaluate the AQP3/PLD2 signaling module in skin diseases, we determined their levels in SCC, basal cell carcinoma (BCC) and psoriasis as compared to normal epidermis. Skin biopsies with the appropriate diagnoses (10 normal, 5 SCC, 13 BCC and 10 plaque psoriasis samples) were obtained from the pathology archives and examined by immunohistochemistry using antibodies recognizing AQP3 and PLD2. In normal epidermis AQP3, an integral membrane protein, was localized mainly to the plasma membrane and PLD2 to the cell periphery, particularly in suprabasal layers. In BCC, AQP3 and PLD2 levels were reduced as compared to the normal-appearing overlying epidermis. In SCC, AQP3 staining was “patchy,” with areas of reduced AQP3 immunoreactivity exhibiting positivity for Ki67, a marker of proliferation. PLD2 staining was unchanged in SCC. In psoriasis, AQP3 staining was usually observed in the cytoplasm rather than in the membrane. Also, in the majority of psoriatic samples, PLD2 showed weak immunoreactivity or aberrant localization. These results suggest that abnormalities in the AQP3/PLD2 signaling module correlate with hyperproliferation in psoriasis and the NMSCs.     

CD109 release from the cell surface in human keratinocytes regulates TGF-β receptor expression, TGF-β signalling and STAT3 activation: relevance to psoriasis

Transforming growth factor (TGF)-β is an important cytokine that negatively regulates keratinocyte proliferation. Deregulation of TGF-β signalling has been reported in psoriasis, where despite increased expression of TGF-β, psoriatic keratinocytes continue to hyperproliferate. Recently, we have identified CD109, a glycosyl phosphatidylinositol (GPI)-anchored protein, as a novel co-receptor and negative regulator of TGF-β signalling. In the current work, we demonstrate that release of CD109 from the cell surface or the addition of CD109 protein results in downregulation of TGF-β signalling and TGF-β receptor expression in human keratinocytes. Moreover, these effects are associated with an increase in phospho-STAT3 levels, enhanced total STAT3 and Bcl-2 expression and an increase in cell growth and survival, suggesting that released/soluble CD109 is able to induce molecular changes that are known to occur in psoriasis. Analysis of CD109 expression in psoriasis patients reveals that CD109 protein expression is markedly decreased in psoriatic epidermis as compared to adjacent uninvolved skin. In contrast, CD109 mRNA expression is unchanged in psoriatic plaques in comparison with normal skin. This raises a possibility that CD109 protein release is enhanced in psoriatic keratinocytes. Furthermore, psoriatic epidermis displays decreased expression of TGF-β receptors, consistent with the results obtained in vitro in keratinocytes with CD109 release or addition of CD109 recombinant protein. Together our findings suggest that aberrant CD109 release from the cell surface in human keratinocytes may induce molecular changes that are usually observed in psoriasis and may explain TGF-β receptor downregulation and decrease in TGF-β signalling in psoriasis.     

The anti‐apoptotic protein G1P3 is overexpressed in psoriasis and regulated by the non‐coding RNA,PRINS

Please cite this paper as: The anti‐apoptotic protein G1P3 is overexpressed in psoriasis and regulated by the non‐coding RNA, PRINS. Experimental Dermatology 2010; 19: 269–278. Abstract: Psoriasis Susceptibility‐Related RNA Gene Induced by Stress (PRINS) is a non‐coding RNA overexpressed in lesional and non‐lesional psoriatic epidermis and induced by stress. Its function in healthy and psoriatic skin is still not known. Here, we report that PRINS regulates G1P3, a gene with anti‐apoptotic effects in keratinocytes. siRNA‐mediated inhibition of PRINS gene resulted in altered cell morphology and gene expression alterations, as demonstrated in a microarray experiment. One of the genes regulated by PRINS ncRNA was G1P3, an interferon‐inducible gene with anti‐apoptotic effects in cancer cells. Interestingly, we found that G1P3 was 400‐fold upregulated in hyperproliferative lesional and ninefold upregulated in non‐lesional psoriatic epidermis compared to healthy epidermis. In vitro, G1P3 protein levels were highest in proliferating keratinocytes and siRNA‐mediated downregulation of G1P3 resulted in increased cell apoptosis. These data indicate that G1P3 inhibits spontaneous keratinocyte apoptosis and hence its high expression in psoriatic skin may contribute to the development of psoriatic lesions. We hypothesize that the deregulation of the PRINS ncRNA may contribute to psoriasis and results in decreased sensitivity to spontaneous keratinocyte apoptosis via the regulation of G1P3.     

Expression of 38-kD cell-surface glycoprotein in transformed human keratinocyte cell lines, basal cell carcinomas, and epithelial germs

In this study, we attempted to identify and characterize transformation-induced cell-surface glycoproteins of human keratinocytes. Therefore, we first searched for glycoproteins which are significantly elevated in human keratinocytes after transformation and immortalization by SV40 virus and which are also found at high levels in keratinocytic cell lines derived from squamous cell carcinomas of the skin. Out of at least 80 different cell-surface antigenic systems of human tumor cells, only three glycoproteins showed elevated expression in transformed keratinocytes. Among these, a 38-kD glycoprotein (gp 38) was highly increased in all transformed keratinocyte cell lines tested, but was not elevated in transformed fibroblasts. The expression of gp 38 was further characterized in normal epidermis and in its benign and malignant hyperproliferative disorders: gp 38 was generally not expressed in normal epidermis and in benign hyperproliferative disorders. In contrast, strong and homogeneous reactivity was found in solid and fibrosing basal cell carcinomas whereas no or low reactivity was detected in squamous cell carcinomas and in those parts of BCC revealing keratotic differentiation. Interestingly, high expression of gp 38 was also found in primary epithelial germs of fetal skin, secondary germ cells of the telogenic hair follicle and secretory tubules of sweat glands. The immunohistologic data suggest that gp 38 is preferentially expressed by epidermal cells which lack squamous and pilosebaceous differentiation.     

TNF-α and serum induce SKALP/elafin gene expression in human keratinocytes by a p38 MAP kinase-dependent pathway

Keratinocytes of inflamed epidermis (psoriasis, wound healing) are hyperproliferative and display an abnormal differentiation programme. This regenerative differentiation pathway is characterized by the induction of genes that are not expressed by keratinocytes in normal skin, such as the cytokeratins CK6, CK16, CK17, and the proteinase inhibitor SKALP/elafin. In the study reported here we investigated the induction and regulation of SKALP expression as a marker for regenerative differentiation in epidermal keratinocytes. Various cytokines and growth factors known to be present in psoriatic epidermis were examined for their ability to induce SKALP gene expression in cultured human keratinocytes. Tumour necrosis factor-alpha (TNF-alpha) and serum were found to be potent inducers of SKALP expression at both the mRNA and the protein levels. SB202190 or SB203580, two specific p38 MAP kinase inhibitors almost completely blocked the induction of SKALP expression by TNF-alpha and serum. These results suggest that in keratinocytes, p38 activity is crucial for the induction of SKALP gene expression. These findings could be relevant for the elucidation of the mechanisms involved in normal and disturbed epidermal differentiation.     

Altered [125I]epidermal growth factor binding and receptor distribution in psoriasis

Stimulation of growth and differentiation of human epidermis by epidermal growth factor (EGF) is mediated by its binding to specific receptors. Whether EGF receptors primarily mediate cell division or differentiation in hyperproliferative disease such as psoriasis vulgaris is unclear. To study the pathogenesis of psoriasis, 4-mm2 punch biopsy specimens of normal, uninvolved, and involved psoriatic skin were assayed for EGF receptors by autoradiographic, immunohistochemical, and biochemical methods. Using autoradiographic and immunohistochemical methods, basal keratinocytes were found to contain the greatest number of EGF binding sites and immunoreactive receptors as compared to the upper layers of the epidermis in both normal epidermis and psoriatic skin. No EGF receptor differences between normal and psoriatic epidermis were observed in this layer. In the upper layers of the epidermis, a 2-fold increase in EGF binding capacity was observed in psoriatic skin as compared with normal thin or thick skin. Biochemical methods indicated that [125I]EGF binding was increased in psoriatic epidermis as compared with similar thickness normal epidermis when measured on a protein basis. Epidermal growth factor was shown to increase phosphorylation of the EGF receptor in skin. EGF receptors retained in the nonmitotic stratum spinosum and parakeratotic stratum corneum may reflect the incomplete, abnormal differentiation that occurs in active psoriatic lesions. Alternatively, retained EGF receptors may play a direct role in inhibiting cellular differentiation in the suprabasal layers.     

Monochromatic excimer light (308 nm): an immunohistochemical study of cutaneous T cells and apoptosis-related molecules in psoriasis

BACKGROUND: Various types of UVB radiation source (290-320 nm) are used in treating psoriasis and their therapeutic mechanism has been attributed to immunosuppressive properties. Recently, a new UVB source generated by a 308-nm excimer laser has been introduced for the treatment of psoriasis. OBJECTIVE: In this study we investigated the immunohistochemical evaluation of T cells and the expression of various apoptosis-related molecules in the psoriatic hyperproliferative skin before and after treatment with 308-nm monochromatic excimer light (MEL). METHODS: Ten patients (three women and seven men), ranging in age from 29 to 79 years, affected by plaque-type psoriasis vulgaris, were treated with MEL. Biopsies from psoriatic lesions of MEL-treated sites were taken before, 24 h and/or 48 h after the first irradiation and analysed by the immunophosphatase alkaline technique (APAAP). RESULTS: MEL treatment was found to cause a significant decrease in the rate of proliferation of keratinocytes and a relevant depletion of T cells in all psoriatic lesions, 48 h after the first irradiation: 308 nm light eliminated T cells from the psoriatic epidermis and also from the dermis, highlighting the ability of this UVB source to penetrate the skin compared with normal UVB and establish direct cytotoxic action on T cells infiltrating skin lesions. Rapid clearing of psoriatic lesions involves potential molecular targets of UVB in T cells including p53, which is upregulated after direct irradiation with 308-nm UVB. Moreover, Bcl-2 expression in healing psoriasis epidermis after MEL treatment is significantly decreased compared with untreated skin and the TUNEL (TdT-mediated dUTP-biotin nick end labelling) technique revealed the presence of relevant apoptotic keratinocytes in the irradiated epidermis. CONCLUSIONS: These results indicate that psoriatic skin after monochromatic excimer light therapy is associated with significant T-cell depletion and alterations of apoptosis-related molecules accompanied by a decreased proliferation index and clinical remission.     

beta-endorphin stimulates cytokeratin 16 expression and downregulates mu-opiate receptor expression in human epidermis

It has been reported that opioid peptides modulate the differentiation of normal human keratinocytes and that mu-opiate receptors are expressed in human epidermis. The regulation of keratinocyte differentiation is particularly important in psoriasis, and one of the markers for hyperproliferative and differentiating skin diseases is cytokeratin 16. The finding that the endogenous mu-opiate receptor ligand beta-endorphin is increased in serum of patients with psoriasis indicates that the mu-opiate system may play an important role in the pathophysiology of the skin. In this study, we addressed the question whether there is a link between mu-opiate receptor regulation and cytokeratin 16 expression in normal and psoriatic skin. Firstly, we demonstrate that beta-endorphin concentrations between 16 and 1000 nM significantly downregulate mu-opiate receptor expression in epidermis of cultured human skin after 48 h. Secondly, we show that beta-endorphin regulates cytokeratin 16 expression in the epidermis of skin organ cultures exposed to 41-125 nM beta-endorphin for 48 h, leading to elevated cytokeratin 16 production. As expected, the expression of cytokeratin 16 was detected primarily in the suprabasal layer. The same pattern was observed in psoriatic lesional skin, i.e., mu-opiate receptor expression was significantly downregulated and cytokeratin 16 expression upregulated. These results suggest that the mu-opiate receptor system and its ligand beta-endorphin are involved in the pathogenesis of psoriasis, especially in terms of differentiation.     

Differential expression of a human endogenous retrovirus E transmembrane envelope glycoprotein in normal, psoriatic and atopic dermatitis human skin

BACKGROUND: Psoriasis is a common inflammatory skin disease characterized by uncontrolled proliferation of keratinocytes and recruitment of T lymphocytes into the skin. The possible role of human endogenous retroviruses (HERVs) in the induction of psoriasis has been suggested, based upon the previous observations of retrovirus-like particles in psoriasis from skin lesional plaques, urine and stimulated lymphocytes. OBJECTIVES: To investigate the expression of HERV-E transmembrane envelope glycoprotein (HERV-E env) in normal, psoriatic and atopic human skin, and to examine the influence of ultraviolet (UV) B irradiation on HERV-E env expression in normal human epidermal keratinocytes. METHODS: The analysis was performed on both skin biopsies and organotypic skin cultures using immunofluorescence and Western immunoblotting. UVB irradiation (312 nm) of cultured normal human keratinocytes was performed using a dose of 30 mJ cm(-2). RESULTS: Positive staining was observed in most of the psoriatic and atopic skin samples, whereas only 15% of the normal skin samples were faintly positive. In addition, the pattern of expression of HERV-E env differed markedly in psoriasis vs. atopy. By Western blotting analysis, two main proteins of 54 and 57 kDa were detected in extracts of normal skin, normal keratinocyte cultures and reconstructed epidermis from psoriatic and normal punch biopsies. An increased level of expression of these proteins was noted in extracts from psoriatic vs. normal reconstructed epidermis. The overexpression of the 57-kDa protein in normal human cultured keratinocytes was dramatically reduced by UVB irradiation. CONCLUSIONS: These data suggest for the first time that HERV-E env is expressed in normal and pathological human skin. Further studies are now required to elucidate the role of such viral proteins in the pathogenesis of psoriasis.     

Examination of Bcl-2, Bcl-X and bax protein expression in psoriasis

BACKGROUND: Psoriasis is an inflammatory skin disease characterized by epidermal hyperplasia and greatly accelerated epidermal turnover. The blockage of normal apoptotic process in the epidermis is one of the factors implicated in the pathogenesis of psoriasis. OBJECTIVE: The purpose of the present study was to elucidate whether bcl-family proteins are significantly involved in the hypothetical antiapoptotic cascade in lesional psoriatic epidermis. METHODS: Twenty-six lesional biopsy samples of 26 patients with psoriasis and five control specimens from normal skin were studied by immunohistochemical method for the differential expression of pro-apoptotic bax and antiapoptotic bcl-2 and bcl-x proteins. RESULTS: Compared with the normal epidermis, bcl-2 expression was significantly reduced, whereas bax and bcl-x were significantly overexpressed in the psoriatic epidermis. The localization of bcl-2/bax/bcl-x proteins in the psoriatic epidermis did not show a significant deviation from that in the normal epidermis. CONCLUSION: These findings indicate a discordant expression of bcl-2 and bax/bcl-x in psoriatic epidermis. Increased bcl-x expression might contribute to the antiapoptotic response in psoriatic keratinocytes. The presence of strong bax expression with a concomitant decrease in bcl-2 expression suggests either a functional defect in bax protein or an inherent/acquired resistance to bax-mediated apoptosis in psoriatic keratinocytes.     

High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis

Recently, it was shown that lesional skin of atopic dermatitis patients expresses low levels of some antimicrobial peptides, compared with psoriasis patients. Here we performed microarray analysis on mRNA from purified lesional epidermal cells of patients with chronic plaque psoriasis and chronic atopic dermatitis, to investigate whether this is a general phenomenon for host defense proteins, and how specific it is for this class of molecules. Microarray data were confirmed on a selected set of genes by quantitative PCR and at the protein level by immunohistochemistry. We found overexpression of many antimicrobial proteins in keratinocytes from psoriatic skin compared with atopic dermatitis skin. Interestingly, we observed that markers of normal differentiation and the activated/hyperproliferative epidermal phenotype were expressed at equal levels. Chronic lesions of psoriasis and atopic dermatitis patients are remarkably similar with respect to cellular proliferation. We conclude that psoriatic epidermis expresses high levels of host defense proteins compared with atopic dermatitis epidermis, and this phenomenon appears to be specific for these proteins. It remains to be investigated whether this is caused by genetic polymorphisms in pathways leading to an epidermal antimicrobial response, or by differences in the cellular infiltrate in psoriasis compared with atopic dermatitis.     

Differential expression of calgranulin A and B in various epithelial cell lines and reconstructed epidermis.

The monoclonal antibody F12, raised against epidermal cells from a psoriatic lesion, decorated antigens highly expressed in psoriatic epidermis and in cultured normal human keratinocytes. In normal human skin, F12 reacted only with follicular keratinocytes. Characterization of the immunoprecipitated antigens by two-dimensional gel electrophoresis revealed their identity with calgranulin A and B. A semiquantitative study with various established epithelial cell lines demonstrated that the expression of calgranulin A and B in hyperproliferative keratinocytes correlates with their potential to undergo terminal differentiation. In epidermis reconstructed in vitro, the antigen expression was stimulated by retinoids and suppressed under vitamin A starvation.     

Hsp72 antigen expression in the proliferative compartment of involved psoriatic epidermis

Oxidative damage to growth regulatory proteins has been implicated in the aetiology of psoriasis. However, the transient synthesis of heat shock proteins has been shown to protect cells against the adverse effects of oxidative and other forms of physiological stress. This study has used an hsp72 monoclonal antibody to measure inducible 72 kDa heat shock protein expression in heat stressed normal human skin and established plaque psoriasis. Hsp72 was detected in the basal and suprabasal layer cells of heat-stressed normal skin, and in 12 involved psoriasis lesions. Hsp72 expression was not detected in unstressed normal skin or in 12 cases of uninvolved psoriasis. Immunoprecipitation and Western blotting of cell lysates from heat stressed normal skin and involved psoriasis lesions confirmed the presence of a 72 kDa polypeptide with hsp72 immunoreactivity. The MIB-1 monoclonal antibody was used to determine the proliferative fraction of normal and involved psoriastic epidermis. The Ki67 antigen was localised to the nuclei of basal and suprabasal layer cells of normal and involved psoriatic epidermis. Involved psoriatic epidermis contained a higher number of proliferating keratinocytes when compared with normal skin. The study has also demonstrated a strong correlation between hsp72 expression and keratinocyte proliferation in involved psoriatic epidermis (r=0.864, p<0.001). We believe that the 72 kDa inducible heat shock protein performs a protective function in the proliferative compartment of normal and involved psoriatic skin.     

Increased calmodulin levels in psoriasis and low Ca++ regulated mouse epidermal keratinocyte cultures

Calcium has been shown to regulate the proliferation of epidermal keratinocytes in vitro. We became interested in the role of the calcium binding protein, calmodulin, in hyperproliferative, low calcium regulated keratinocytes in vitro and in the in vivo hyperproliferative state, psoriasis. Calmodulin levels were measured by radioimmune assay in neonatal mouse keratinocytes grown in 0.02 mM calcium (hyperproliferative) and 1.2 mM calcium (normal) media, and in cells that had been grown in low calcium medium and then switched to normal calcium. On a whole culture basis the normal cells had more calmodulin than the low calcium cells. However, when low calcium monolayers were compared to the normal basal monolayer, the low calcium hyperproliferative cells had more calmodulin. Cells that were switched from 0.02 mM calcium to 1.2 mM calcium showed increasing calmodulin levels over time. Psoriatic plaques contained 2-3 times more calmodulin than the skin of normal controls when examined on a per micrograms of DNA, per micrograms of protein, and per gram of wet weight basis. Adjacent uninvolved psoriatic skin also had significantly elevated calmodulin levels in all data bases except per microgram of protein/cm2. These data suggest that increased calmodulin levels are associated with epidermal hyperproliferation and/or with the state of differentiation.     

Psoriasiform architecture of murine epidermis overlying human psoriatic dermis transplanted onto SCID mice

Preliminary observations in a xenogeneic SCID mouse transplantation model indicated that murine epidermis overgrows human dermis from psoriatic skin but not that form normal skin. To investigate the effect of peripheral blood mononuclear cells on the differentiation of murine keratinocytes, we transplanted involved and uninvolved full-thickness skin from patients with psoriasis onto SCID mice and followed this with repeated subcutaneous injections of cells suspended in patient serum. After 6 weeks grafts were analysed morphologically and immunohistochemically. The epidermis in grafts from clinically uninvolved skin appeared normal. The persistence of a psoriasiform epidermis was noted in all grafts from affected sites despite a lack of lymphocytic infiltration. Staining for human and mouse MHC class I antigens revealed the murine origin of keratinocytes forming the psoriasiform epidermis, while the human dermis was retained. Our observations indicate that the defect underlying the pathogenesis of psoriasis is most likely located in the dermal rather than the epidermal compartment. This xenogeneic transplantation model may be useful for future studies of the pathogenesis and treatment of psoriasis.     

Reciprocal altered expression of T-cadherin and P-cadherin in psoriasis vulgaris

BACKGROUND: The most characteristic change in psoriasis vulgaris is markedly increased, persistent keratinocyte proliferation. The underlying mechanism of excessive epidermal growth is controversial. We previously found and reported that T-cadherin was expressed in keratinocytes and confined to the basal layer of mouse and human skin. Invasive cutaneous squamous cell carcinoma showed a loss of T-cadherin expression. Another study showed that T-cadherin was a negative growth regulator of epidermal growth factor in T-cadherin transfectant neuroblastoma cells. OBJECTIVES: To obtain insight into the role of T-cadherin in keratinocyte proliferation and to investigate further the pathogenesis of psoriasis vulgaris, we examined the expression of T-cadherin, as well as E- and P-cadherin, in psoriasis vulgaris. METHODS: Four untreated active psoriatic skin samples from psoriasis vulgaris patients and four normal human skin samples from plastic surgery were collected, cryosectioned and immunohistochemically stained by antihuman T-, P- and E-cadherin antibodies. Further, the immunofluorescence intensities of T- and P-cadherin on the basal layer of the epidermis were quantitatively measured by the histogram function of LSM 510 software installed in a Zeiss laser scanning confocal microscope. The data were statistically analysed by Student's t-test. RESULTS: It was observed that T-cadherin was weakly and discontinuously expressed on the basal layer of psoriatic skin, while it was intensively expressed on all basal keratinocytes in normal human skin. In contrast, P-cadherin was strongly expressed throughout the entire epidermal layer in psoriatic skin samples, although its expression is restricted to the basal cell layer in normal human skin. There were no obvious differences in E-cadherin expression between normal human skin and psoriatic skin. Statistical analyses showed that the immunofluorescence intensity of T-cadherin in the basal cell layer of psoriatic skin (35 +/- 9.08) was significantly decreased compared with that in normal human skin (131.75 +/- 3.49, P = 2.46 x 10(-6)). There was a significant increase (P = 0.00139) in the immunofluorescence intensity of P-cadherin in the basal layer of psoriatic skin (68.25 +/- 12.13) compared with normal human skin (26 +/- 4.90). CONCLUSIONS: The present study demonstrates that there is downregulation of T-cadherin expression and upregulation of P-cadherin expression in psoriatic skin, which are considered to be involved in the hyperproliferation of keratinocytes in psoriasis vulgaris.