Under-expression of VHL and over-expression of HDAC-1, HIF-1alpha, LL-37, and IAP-2 in affected skin biopsies of patients with psoriasis.

BACKGROUND: A feature of psoriasis is the rapid proliferation of keratinocytes, during which apoptosis is blocked and angiogenesis starts. It is known that tumor hypoxic cells produce histone deacetylase-1 (HDAC-1), which up-regulates hypoxia-inducible factor-1alpha (HIF-1alpha) and down-regulates von Hippel-Lindau (VHL) protein by up-regulating vascular endothelial growth factor (VEGF) expression. It has been reported recently that the porcine peptide PR39 (homologous to human LL-37) has angiogenic and antiapoptotic activity. Thus, LL-37, induced by insulin-like growth factor-1 (IGF-1), could help in the production of VEGF. PR39 also induces the expression of inhibitor of apoptosis protein-2 (IAP-2), which blocks apoptosis. The purpose of this work was to analyze whether these genes and their proteins are expressed in psoriatic biopsies. METHODS: Using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) messenger RNA (mRNA) expression and immunohistochemical staining, we studied VHL, IAP-2, and related genes in skin biopsies from psoriatic patients and healthy subjects. RESULTS: An over-expression of the mRNA for HDAC-1, HIF-1alpha, LL-37, and IGF-1 in psoriatic skin, in comparison with skin from healthy subjects, was found. The antiangiogenic VHL mRNA and protein were under-expressed in psoriatic skin and highly expressed in healthy skin. The antiapoptotic IAP-2 was over-expressed in dermal endothelial cells from psoriatic skin. The pro-apoptotic Bax, Fas, and FasL mRNAs were expressed. CONCLUSIONS: These findings suggest that there could be an association of HDAC-1, HIF-1alpha, LL-37, VHL, and IAP-2 with angiogenic and apoptotic mechanisms in psoriasis.

IgG class antibodies from psoriasis patients recognize the 60-KDa heat-shock protein of Streptococcus pyogenes.

BACKGROUND: We have previously found that psoriatic patients have IgG autoantibodies that recognize lesions but not autologous normal skin. The reactivity of the autoantibodies can be adsorbed with streptococcal antigens. METHODS: IgG antibodies were determined by immunoblot and ELISA to streptococcal antigens and by ELISA to the recombinants HSP60Sp, HSP70Sp, HSP60Ec and HSP60Hu, in plaque (PP) and guttate (GP) psoriasis patients, in healthy subjects (HC) and in individuals with streptococcal throat infections and high ASO titers, but without history of dermatological disease (ISp). RESULTS: We found by immunoblot that the IgG response to 71-, 60-, and 14-kDa protein fractions of Streptococcus pyogenes is important in psoriasis. We also found by ELISA that the response to the rHSP60Sp in PP was higher than in all the other three groups studied (P < 0.05) with an odds ratio of 11.11 (CI95% of 4.33-28.49). The PP infected with S. pyogenes had higher titers of the antirHSP60Sp, high ASO, and high PASI. The PP patients did not significantly recognize the HSP60Ec or the HSP60Hu. The GP patients had a higher response to the rHSP60Sp than the healthy controls or ISp patients (P < 0.05) but showed no association with the disease. The response of the ISp patients to the HSP60Sp was similar to the healthy controls. The response to the rHSP70Sp was similar in the PP patients and the healthy controls. CONCLUSION: Results suggest that a high response to the HSP60Sp could be associated with the chronic form of psoriasis.

Interleukin-13 receptor in psoriatic keratinocytes: overexpression of the mRNA and underexpression of the protein.

Although several cytokines and their receptors have been involved in the development of psoriasis, the etiology is still unknown. In this study we looked for genes possibly involved in the disease by the reverse transcription-polymerase chain reaction differential display technique in lesional and nonlesional skin biopsies from psoriatic patients. We found the mRNA of the alpha1 chain of the interleukin-13 receptor expressed differentially in psoriatic biopsies. By reverse transcription-polymerase chain reaction, we confirmed an overexpression of the alpha1 chain of the IL-13 receptor and alpha chain of the interleukin-4 receptor mRNA in lesional skin psoriatic biopsies, when compared with skin biopsies from healthy subjects (p<0.01). The nonlesional skin obtained from a region close to a lesional zone in psoriatic patients presented also an overexpression of these mRNA in 50% of the samples. Interleukin-13 and interleukin-4 were not detected either as mRNA or as the proteins in any of the biopsies from psoriatic patients or healthy subjects. A monoclonal antibody to the alpha1 chain of the interleukin-13 receptor detected the receptor in the epidermal keratinocytes of psoriatic patients and of healthy subjects; however, the positive antibody reaction was stronger in skin tissue from healthy subjects than in psoriatic lesional skin tissue (p<0.01), although the mRNA was overexpressed. As interleukin-13 is a pleiotropic immunoregulatory cytokine with a variety of effects on different cell types, including monocytes, B lymphocytes, mast cells, and keratinocytes, we suggest, based on our results, that the interleukin-13 receptor possibly plays an important part in the early inflammatory process of psoriasis; however, its function is lost in the psoriatic keratinocytes.

Diacronía del jiote / Diachrony of the so-called jiote skin lesion

Se señala la importancia del estudio nosológico de las enfermedades tradicionales, tomando en cuenta la ventaja que ofrece la dermatología por su enfoque morfológico y analizando el término jiote a través del tiempo (diacronía), lo tomamos como ejemplo representativo de las dermatosis tradicionales. Asi mismo, con base en un estudio de cien dermatosis referidas por los pacientes como jiotes, se postula la existencia del síndrome jiote

Deflazacort+ en el tratamiento de los pénfigos: estudio piloto / Deflazacort in the treatment of pemphigus: pilot study

Se reportan cuatro casos de pacientes del sexo femenino con pénfigo tratado con deflazacort (1.25 mg/kg/día), glucocorticoide semejante a la prednisona, pero con menos efectos en el metabolismo del calcio y carbohidratos. Se realizaron evaluaciones de variables de eficacia, como días para el control (ausencia de nuevas ampollas), y de seguridad, como glucemia y densitometría ósea. En un promedio de 28.7 días se logró el control del pénfigo con una dosis total promedio de deflazocort de 2,3175 mg. El deflazacort resultó eficaz en el control del pénfigo, con mínimos efectos secundarios. Son deseables ensayos clínicos controlados comparativos con prednisona y de mayor seguimiento