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Prurigo pigmentosa (PP), a rare inflammatory disease of the skin, is mostly reported in the ethnic Japanese population. Its pathogenesis remains unclear. The chronic and recurrent nature of PP implies a possible role of viral infection in the pathogenesis. The anti-inflammatory mechanism of doxycycline, which is well documented as a good treatment for PP, is related to the suppression of interleukin expression. We identified and retrospectively analyzed 16 biopsy-proven and criteria-matched patients over a seven year period at a single medical center. DNA extracted from formalin-fixed, paraffin-embedded specimens was analyzed for herpes simplex virus-1 (HSV-1), HSV-2, and human herpes virus-6 (HHV-6) DNA by polymerase chain reaction. Immunohistochemistry was performed to determine the interleukin-6 (IL-6) and interleukin-8 (IL-8) expression in PP skin lesions. Clinicopathological findings in the ethnic Chinese population are similar to those reported in Japanese studies. All patients had a good response to doxycycline treatment, with a mean duration of use of 2.4 weeks. However, recurrence was noted in six patients. HSV-1, HSV-2, and HHV-6 DNA in PP skin lesions were negative. Immunohistochemistry showed IL-6 ( P = 0.035) to be more strongly expressed in PP skin lesions. There was no statistical significance of elevated IL-8 expression in PP ( P = 0.123). Prurigo pigmentosa is not uncommon in the ethnic Chinese population. There was no evidence of herpes virus DNA in PP skin lesions. Increased expression of IL-6 in PP skin lesions may explain the effects of doxycycline in terms of its anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

An abstract of the article "The Forkhead Transcription Factor FOXO3a Increases Phosphoinositide-3 Kinase/Akt Activity in Drug-Resistant Leukemic Cells through Induction of PIK3CA Expression," by Rosaline C.-Y. Hui, Ana R. Gomes, Christina T. Karadedou, and Joanna R. Costa is presented.

Epstein-Barr virus (EBV) infection is associated with the development of many B-cell lymphomas, including Burkitt's lymphoma, Hodgkin's lymphoma, and posttransplant lymphoproliferative disease. The virus alters a diverse range of cellular molecules, which leads to B-cell growth and immortalization. This study was initiated to investigate the interplay between EBV and a proapoptotic transcription factor target, FoxO1. In this report, we show that EBV infection of B cells leads to the downregulation of FoxO1 expression by phosphatidylinositol 3-kinase-mediated nuclear export, by inhibition of FoxO1 mRNA expression, and by alteration of posttranslational modifications. This repression directly correlates with the expression of the FoxO1 target gene Bcl-6 and inversely correlates with the FoxO1-regulated gene Cyclin D2. Expression of the EBV genes for latent membrane protein 1 and latent membrane protein 2A decreases FoxO1 expression. Thus, our data elucidate distinct mechanisms for the regulation of the proapoptotic transcription factor FoxO1 by EBV. [ABSTRACT FROM AUTHOR]

Leukemic transformation often requires activation of protein kinase B (PKB/c-Akt) and is characterized by increased proliferation, decreased apoptosis, and a differentiation block. PKB phosphorylates and inactivates members of the FOXO subfamily of Forkhead transcription factors. It has been suggested that hyperactivation of PKB maintains the leukemic phenotype through actively repressing FOXO-mediated regulation of specific genes. We have found expression of the transcriptional repressor Id1 (inhibitor of DNA binding 1) to be abrogated by FOXO3a activation. Inhibition of PKB activation or growth factor deprivation also resulted in strong down-regulation of Id1 promoter activity, Id1 mRNA, and protein expression. Id1 is highly expressed in Bcr-Abl-transformed K562 cells, correlating with high PKB activation and FOXO3a phosphorylation. Inhibition of Bcr-Abl by the chemical inhibitor ST1571 resulted in activation of FOXO3a and down-regulation of Id1 expression. By performing chromatin immunoprecipitation assays and promoter-mutation analysis, we demonstrate that FOXO3a acts as a transcriptional repressor by directly binding to the Id1 promoter. ST1571 treatment, or expression of constitutively active FOXO3a, resulted in erythroid differentiation of K562 cells, which was inhibited by ectopic expression of Id1. Taken together our data strongly suggest that high expression of Id1, through PKB-mediated inhibition of FOXO3a, is critical for maintenance of the leukemic phenotype. [ABSTRACT FROM AUTHOR]