Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thermal balneotherapy with Comano spa's water (CW; Trentino, Italy) is used for psoriasis and other skin disorders but the mechanism(s) of action of this hypotonic water are unknown. Since skin psoriatic manifestations are thought to be angiogenesis-dependent, we assessed CW's effects on the expression and release of VEGF-A protein isoforms by cultured human lesional keratinocytes isolated from skin biopsies performed in 9 patients. Confluent, psoriatic keratinocytes were exposed for 11 days to DMEM, whose chemicals had been dissolved in either deionised water (DW-DMEM, controls) or CW (CW-DMEM, treated cells). As detected by Western immunoblotting (WB), incubation in CW-DMEM elicited, with respect to DW-DMEM, an increase in intracellular and/or cell-bound L-VEGF-A189 and L-VEGF-A165 48 kDa protein isoforms with no concurrent change in L-VEGF-A121 and L-VEGF-A165 45 kDa proteins. Moreover, WB analysis of the secreted VEGF-A (sVEGF-A) proteins showed that the 20 and 15 kDa bands corresponding to different VEGF-A isoforms were directly and remarkably reduced in keratinocyte-conditioned CW-DMEM vs. DW-DMEM. Thus, CW interferes with VEGF-A isoform expression and secretion by the psoriatic keratinocytes. These effects would reduce all VEGF-A-mediated angiogenic, vessel permeabilising, and chemotactic effects, thereby at least in part explaining the beneficial actions of CW balneotherapy on the clinical manifestations of psoriasis.
Int J Mol Med 2006 Jul
PMID:Comano's (Trentino) thermal water interferes with the expression and secretion of vascular endothelial growth factor-A protein isoforms by cultured human psoriatic keratinocytes: a potential mechanism of its anti-psoriatic action. 1678 51

Psoriasis is a common cutaneous disorder characterized by abnormal epidermal differentiation, proliferation and inflammation mediated by dermal infiltrates, such as T cells, neutrophils, dendritic cells and macrophages. There are renewed interest in the role of components of the innate immune system. Cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6, and -1beta involved in pathogenic phenomena in psoriasis are known as inducers of the acute phase response. Among the large group of acute phase reactants, C-reactive protein (CRP) and fibrinogen are of special interest in psoriasis. The PTX-3, a long pentraxin sharing similarities with the classical short proteins. Thus, considering the numerous biological roles of inflammatory cytokines and their relationship with inflammatory markers, such as CRP and fibrinogen we have investigated the role of PTX3 in psoriasis. To this aim PTX3, TNF-alpha, IL-6 and IL-1beta in plasma and in monocytic cultures by enzyme linked immunosorbent assay (ELISA) in 44 patients including severe and mild psoriasis were measured. An increased production of PTX3, both in supernatant of purified monocytes and in plasma from patients with severe psoriasis, was found. The significant correlation, between cellular production and plasma levels of PTX3 in psoriasis was found as a sign of cellular activation by monocytes/macrophages that first infiltrate the psoriatic lesion. In severe psoriasis, a significant correlation between psoriasis area and severity index (PASI) score and TNF-alpha and IL-6 levels in both supernatant of monocytes and plasma was found. In contrast, no correlation was found for IL-1beta. By immunohistochemistry and immunofluorescence, a strong PTX3 staining in fibroblasts, endothelial cells and monocytes/macrophages in severe psoriatic lesional skin was detected. Finally, a positive correlation between PTX3 and disease activity of psoriasis was observed as PASI score was elevated. These findings suggest that PTX3 could be used as a further marker of disease activity of psoriasis.
Int J Mol Med 2006 Sep
PMID:Long pentraxin 3: a marker of inflammation in untreated psoriatic patients. 1686 25

It has previously been reported that pemphigoid coexists with psoriasis more frequently than it could be predicted on the basis of random distribution in the general population. In this study we present three psoriatic patients who developed tense blisters, which most likely were not provoked by anti-psoriatic treatment. Diagnosis of bullous pemphigoid in these cases was established by an overlay antigen mapping technique by laser confocal microscopy, immunoblotting and ELISA. In the context of these cases and the literature, we also discuss possible reasons for the coexistence of psoriasis and pemphigoid as well as selected aspects of diagnosis and therapy of patients simultaneously suffering from these two diseases.
Int J Mol Med 2006 Oct
PMID:Coexistence of psoriasis and pemphigoid--only a coincidence? 1696 14

Thermal balneotherapy with Comano's spa water (CW; Trentino, Italy) is used for psoriasis and other skin disorders but its mechanisms of action are mostly unknown. Previously, we showed that CW can interfere with the expression and secretion of various VEGF-A isoforms by cultured human psoriatic epidermal keratinocytes. In this study, confluent cultures of IL-6-hypersecreting keratino-cytes isolated from 6 psoriatic patients were exposed for 11-15 days to DMEM, the chemicals of which had been dissolved in either deionised water (DW-DMEM, controls) or CW (CW-DMEM, treated cells). As detected by means of immunocytochemistry, Western immunoblotting, and ELISA assays, the intracellular levels and secretion rates of IL-6 were drastically curtailed in the CW-DMEM-incubated keratinocytes and in their cell-conditioned media. A nearly maximal inhibition of IL-6 release had already been induced by a CW fraction in the DMEM as low as 25%. CW exposure also promptly, intensely, and persistently down-regulated the expression of cytokeratin-16 (CK-16), a marker associated with keratinocyte psoriatic phenotype. Hence, CW balneotherapy may beneficially affect the clinical manifestations of psoriasis via an attenuation of the local deregulation of several cytokines/chemokines, including IL-6 and VEGF-A isoforms, and of a concurrent, abnormal cell differentiation program entailing the expression, amongst other proteins, of CK-16.
Int J Mol Med 2006 Dec
PMID:Comano's (Trentino) thermal water interferes with interleukin-6 production and secretion and with cytokeratin-16 expression by cultured human psoriatic keratinocytes: further potential mechanisms of its anti-psoriatic action. 1708 10

The HCR gene, officially called Coiled-Coil alpha-Helical Rod protein 1 (CCHCR1), located within the major psoriasis susceptibility locus PSORS1, is a plausible candidate gene for the risk effect. Recently, CCHCR1 was shown to promote steroidogenesis by interacting with the steroidogenic acute regulator protein (StAR). Here, we examined the role of CCHCR1 in psoriasis and cutaneous steroid metabolism. We found that CCHCR1 and StAR are expressed in basal keratinocytes in overlapping areas of the human skin, and CCHCR1 stimulated pregnenolone production in steroidogenesis assay. Overexpression of either the CCHCR1*WWCC risk allele or the non-risk allele enhanced steroid synthesis in vitro. Furthermore, the cytochrome P450scc enzyme was expressed in human keratinocytes and was induced by forskolin, a known activator of steroidogenesis, and forskolin also upregulated CCHCR1. CCHCR1 has an altered expression pattern in lesional psoriatic skin compared to normal healthy skin, suggesting its dysregulation in psoriasis. We found that the expression of CCHCR1 is downregulated twofold at the mRNA level in cultured non-lesional psoriatic keratinocytes when compared to non-psoriatic healthy cells. Our results also suggest a connection between CCHCR1 and vitamin D metabolism in keratinocytes. The expression of the vitamin D receptor (VDR) gene was lower in non-lesional psoriatic keratinocytes than in healthy cells. Furthermore, Vdr expression was downregulated in the keratinocytes of mice overexpressing the CCHCR1*WWCC risk allele when compared to keratinocytes from mice with the non-risk allele of CCHCR1. Finally, we demonstrate that other agents relevant for psoriasis and/or the regulation of steroidogenesis influence CCHCR1 expression in keratinocytes, including insulin, EGF, cholesterol, estrogen, and cyclosporin A. Taken the role of steroid hormones, including vitamin D and estrogen, in cell proliferation, epidermal barrier homeostasis, differentiation, and immune response, our results suggest a role for CCHCR1 in the pathogenesis of psoriasis via the regulation of skin steroid metabolism.
J Mol Med (Berl) 2007 Jun
PMID:The CCHCR1 (HCR) gene is relevant for skin steroidogenesis and downregulated in cultured psoriatic keratinocytes. 1722 Dec 18

Both calcitriol and UVB radiation exert potent antipsoriatic effects. We hypothesize that the therapeutical effect of UVB radiation may be attributed at least in part to UVB-triggered cutaneous synthesis of calcitriol. The optimum wavelength for initiation of the vitamin D(3) pathway was found to be in the range of 300+/-5 nm in vitro and in vivo. The narrowband Philips TL-01 lamp which is commonly used as UVB source for phototherapy of psoriasis has maximum spectral irradiance at around 311 nm which is presumed to be, however, of lesser importance in photochemical activation of the vitamin D(3) pathway. The aim of this study was to compare the vitamin D(3) and calcitriol-inducing potential of UVB from the TL-01 lamp with that of monochromatic UVB at 300+/-2.5 nm and 310+/-2.5 nm in organotypic cultures of keratinocytes supplemented with 25 microM 7-DHC. We found that maximum calcitriol-generating capacity of the TL-01 lamp at 500 mJ/cm(2) and 16 h after irradiation still amounts up to 44% of that found after monochromatic irradiation at 300+/-2.5 nm and 30 mJ/cm(2). Thus, the antipsoriatic effect of UVB emitted from the TL-01 lamp may, at least in part, based on the antiproliferative and prodifferentiative action of newly synthesized calcitriol on epidermal keratinocytes.
J Steroid Biochem Mol Biol 2007 Mar
PMID:The UVB-induced synthesis of vitamin D3 and 1alpha,25-dihydroxyvitamin D3 (calcitriol) in organotypic cultures of keratinocytes: effectiveness of the narrowband Philips TL-01 lamp (311 nm). 1723 83

Peptech is developing PMX-53, a complement C5a inhibitor for the potential treatment of inflammatory disorders, including rheumatoid arthritis and psoriasis. Phase Ib/IIa clinical trials have been completed for both indications.
Curr Opin Mol Ther 2006 Dec
PMID:Drug evaluation: the C5a receptor antagonist PMX-53. 1724 89

Thermal balneotherapy with Comano's spa water (CW; Trentino, Italy) is beneficial for psoriasis and other skin disorders but its operative mechanisms are largely unknown. Previously, we showed that CW interferes with the production and secretion of IL-6 and various VEGF-A isoforms and with CK-16 expression by cultured human psoriatic keratinocytes. In this study, confluent cultures of epidermal keratinocytes isolated from the lesional areas of 9 psoriatic patients were exposed for 11-13 days to DMEM, whose chemicals had been dissolved in either deionised water (DW-DMEM, controls) or CW (CW-DMEM, treated cells), in order to assess the expression and secretion of TNF-alpha and IL-8 by such cells. The results gained by means of immunocytochemistry, Western immunoblotting (WB), and ELISA assays showed that CW exposure significantly down-regulated the intracellular levels of TNF-alpha, a key inducer of IL-8, IL-6, and other chemokines. However, no assayable TNF-alpha secretion occurred in keratinocyte-conditioned DW- and CW-DMEM samples. Moreover, the intracellular levels and secretion rates of IL-8 were also markedly reduced in the protein extracts and conditioned media of CW-DMEM-incubated keratinocytes. Notably, the most effective inhibition of IL-8 secretion was elicited by a 25% CW fraction in the DMEM. Altogether, our findings indicate that by attenuating at lesional skin sites the deregulated production and secretion of a cascade of several cytokines and chemokines (e.g. TNF- alpha, IL-8, IL-6, and various VEGF-A isoforms), and by offsetting the keratinocytes' abnormal differentiation program entailing CK-16 expression, CW balneotherapy may beneficially influence the clinical manifestations of psoriasis.
Int J Mol Med 2007 Mar
PMID:Comano's (Trentino) thermal water interferes with tumour necrosis factor-alpha expression and interleukin-8 production and secretion by cultured human psoriatic keratinocytes: yet other mechanisms of its anti-psoriatic action. 1727 83

TNF-alpha induces some proinflammatory cytokines including IL-1beta, IL-6, IL-8, and itself by activation of NF-kappaB or MAPKs (p38, JNK, ERK). These cytokines play important roles in various inflammatory skin diseases, such as psoriasis. Recently it was also reported that expression of cyclin E is up-regulated by ERK pathway after TNF-alpha treatment. However, it was unknown whether curcumin, showing inhibitory effects on NF-kappaB and MAPKs, attenuates the expression of TNF-alpha-induced IL-1beta, IL-6, IL-8, and TNF-alpha as well as cyclin E expression in HaCaT cells. In this study, we investigated the inhibitory effect of curcumin on expression of proinflammatory cytokines and cyclin E in TNF-alpha-treated HaCaT cells. We found that curcumin inhibited the expression of TNF-alpha-induced IL-1beta, IL-6, and TNF-alpha, but not IL-8, in TNF-alpha-treated HaCaT cells as well as the TNF-alpha-induced cyclin E expression. In addition, curcumin inhibited the activation of MAPKs (JNK, p38 MAPK, and ERK) and NF-kappaB in TNF-alpha-treated HaCaT cells. Taken together, curcumin exerts anti-inflammatory and growth inhibitory effects in TNF-alpha-treated HaCaT cells through inhibition of NF-kappaB and MAPK pathways.
Int J Mol Med 2007 Mar
PMID:Curcumin attenuates the expression of IL-1beta, IL-6, and TNF-alpha as well as cyclin E in TNF-alpha-treated HaCaT cells; NF-kappaB and MAPKs as potential upstream targets. 1727 96

Atopic dermatitis (AD) is a strongly heritable, chronic relapsing dermatosis that frequently co-occurs with other atopic phenotypes including asthma and allergic rhinitis (the so-called atopic triad disorders). However, despite high levels of co-morbidity, relatively low levels of genomic co-incidence have been observed between atopic triad disorders. Conversely, current mapping data have revealed a striking pattern of co-localisation between AD disease loci and those mapped using another chronic dermatological disease - psoriasis. In this review, we examine the evidence for co-localisation between AD and a range of atopic, infectious, inflammatory and autoimmune diseases, and consider the implications of these data for the AD disease concept and future research in the field.
Expert Rev Mol Med 2007 Apr 03
PMID:Atopic dermatitis: insights from linkage overlap and disease co-morbidity. 1740 13


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