The incidence of skin manifestations by dermatophytes in patients with psoriasis

Thirty-four psoriatic patients (23 males, 11 females) were found to have skin manifestations of dermatophyte infection. Tinea pedis was observed in 20 cases, tinea cruris in 6 and tinea mannum in 2. T. rubrum was the causative agent in all of these with the exception of 2 cases caused by E. floccosum. Lesions of tinea corporis were found intermingled with psoriatic plaques in various areas of the body skin in 6 patients (4 males, 2 females); T. rubrum was isolated from 5 of these and M. canis from one. Twenty-one of these psoriatic patients also had lesions caused by C. albicans in the toe-webs and interdigital aspects of the fingers, the latter being associated with paronychia in 9 cases. These findings indicate that we should remain aware of the possibility of fungus manifestations in patients with psoriasis, which would not appear to be an exceptional occurrence.     

Expression of antimicrobial peptides and proteins in etanercept-treated psoriasis patients

Recent papers highlight the role of dysregulated expression of antimicrobial peptides and proteins (AMPs) in the pathogenesis of psoriasis. Etanercept, a blocker of the pro-inflammatory cytokine tumour necrosis factor-α (TNF-α), is effective in the treatment of psoriasis. We aimed to evaluate the expression profiles of AMPs in psoriatic skin before and after a 6-week course of etanercept therapy. We included 12 psoriasis patients who underwent medium-dose etanercept treatment for 6weeks. At baseline and at the end of therapy immunohistochemistry from lesional skin was performed for psoriasin, LL-37, and human ?-defensin 2 (hBD-2). After 6-week treatment, the modified psoriasis area and severity index significantly decreased from 37.5±5.9 to 14±13.4. Lesional immunoreactivity scores of psoriasin, LL-37, and hBD-2 also significantly decreased after a 6-week course of etanercept. We have demonstrated that etanercept-induced improvement of psoriasic lesions is associated with a significant decline of AMP protein expression.     

Expression of retinoic acid receptor genes in keratinizing front of skin

We found, by an in situ hybridization method with riboprobes synthesized from human cDNA of the retinoic acid receptor (RAR), that the RAR genes (predominantly gamma-subtype) are intensively expressed in the epidermis of normal and psoriasic human skins, and also in keratinizing fronts of 4-day-old mouse skins, nail matrices and hair follicles. Thus, target cells of retinoic acid in the skins are concluded to be keratinocytes, which is quite consistent with the fact that retinoic acid regulates keratinization of epidermis in vivo and also modulates expression of the keratin gene in vitro.     

Cytokines in skin lesions of psoriasis

Cytokine levels were compared in aqueous extracts of stratum corneum from psoriatic lesions and normal heel. Samples from heel contained high levels of interleukin-1 alpha (IL-1 alpha) and beta measured in immunoassays, although only the IL-1 alpha was biologically active. No other cytokines could be detected in heel samples. Interleukin-1 (IL-1) levels were dramatically reduced in lesional samples. A neutrophil chemoattractant was found in all lesional extracts, and was demonstrated to be mainly interleukin-8 (IL-8) using a specific neutralizing antiserum. Tumor necrosis factor alpha (TNF-alpha) and beta (TNF-beta), and interferon alpha (IFN-alpha) and gamma (IFN-gamma) were detected in lesional extracts using immunoassays, however, no equivalent biological activities could be detected. Interleukins 2 (IL-2), 4 (IL-4), and 6 (IL-6), granulocyte and granulocyte/macrophage colony stimulating factor (GM-CSF), could not be detected in any samples. IL-8 is therefore the only biologically active cytokine shown in this study to be elevated in psoriatic lesional extracts, and may therefore play a role in the pathogenesis of the disease.     

Expression of genes coding melatonin and serotonin receptors in rodent skin

Targeted search for expression of melatonin and serotonin receptors genes in the skin of C57BL/6J mice showed expression of MT1B (but not MT1A). Mouse skin and hamster melanomas also expressed 5HT2B and 5HT7. We identified two novel isoforms of MT1A and 5HT7.     

Identical TCR beta-chain rearrangements in streptococcal angina and skin lesions of patients with psoriasis vulgaris

Tonsillar infection with Streptococcus pyogenes may induce several nonsuppurative autoimmune sequelae. The precise pathogenetic mechanisms behind this clinically well-established association are still unresolved. Using TCR analysis, we sought to identify a link between streptococcal tonsillitis and the T cell-mediated autoimmune response in psoriasis. Three patients with streptococcal-induced psoriasis underwent tonsillectomy. Using size spectratyping and sequencing of TCR beta-chain variable region gene (TCRBV) rearrangements, we compared the TCR usage of psoriatic skin lesions, blood, tonsils, and tonsillar T cells fractionated according to the expression of the skin address in "cutaneous lymphocyte-associated Ag" (CLA). TCRBV-size spectratype analysis of the blood lymphocytes, tonsils, and the CLA-negative tonsillar T cells revealed largely unselected T cell populations. Instead, TCRBV gene families of the psoriatic lesions and skin-homing CLA-positive tonsillar T cells displayed highly restricted spectratypes. Sequencing of TCRBV cDNA identified various clonal TCRBV rearrangements within the psoriatic lesions that indicated Ag-driven T cell expansion. Several of these clonotypes were also detected within the tonsils and, in one of the patients, within the small subset of CLA-positive tonsillar T cells, suggesting that T cells from the same T cell clones were simultaneously present within skin and tonsillar tissue. Because after tonsillectomy psoriasis cleared in all three patients our observations indicate that T cells may connect psoriatic inflammation to streptococcal angina. They suggest that the chronic streptococcal immune stimulus within the tonsils could act as a source for pathogenic T cells in poststreptococcal disorders, and they may help to explain why eliminating this source with tonsillectomy may improve streptococcal-induced sequelae.     

Expression profile of genes identified in human spermatogonial stem cell‐like cells using suppression subtractive hybridization

Spermatogenesis is the process by which testicular spermatogonial stem cells (SSCs) self‐renew and differentiate into mature sperm in the testis. Maintaining healthy spermatogenesis requires proper proliferation of SSCs. In this study, we sought to identify factors that regulate the proliferation of SSCs. Human SSC (hSSC)‐like cells were isolated from azoospermic patients by a modified culture method and propagated in vitro. After four to five passages, the SSC‐like cells spontaneously ceased proliferating in vitro, so we collected proliferating (P)‐hSSC‐like cells at passage two and senescent (S)‐hSSC‐like cells at passage five. Suppression subtractive hybridization (SSH) was used to identify genes that were differentially expressed between the P‐hSSC‐like and S‐hSSC‐like cells. We selected positive clones up‐regulated in P‐hSSC‐like cells using SSH and functionally characterized them by reference to public databases using NCBI BLAST tools. Expression levels of genes corresponding to subtracted clones were analyzed using RT‐PCR. Finally, we confirmed the differential expression of 128 genes in positive clones of P‐hSSC‐like cells compared with S‐hSSC‐like cells and selected 23 known and 39 unknown clones for further study. Known genes were associated with diverse functions; 22% were related to metabolism. Fifteen of the known genes and two of the unknown genes were down‐regulated after senescence of hSSC‐like cells. A comparison with previous reports further suggests that known genes selected, SPP1, may be related to germ cell biogenesis and cellular proliferation. Our findings identify several potential novel candidate biomarkers of proliferating‐ and senescencet‐hSSCs, and they provide potentially important insights into the function and characteristics of human SSCs. J. Cell. Biochem. 110: 752–762, 2010. © 2010 Wiley‐Liss, Inc.     

Nomenclature for identified pigmentation genes in the mouse

More than 90 different loci influence pigmentation in the mouse. During the past few years, an increasing number of genes have been identified, and assigned to the corresponding coat color loci and pigmentation mutants. As a consequence, different names have been used in publications for loci, genes and corresponding proteins. In the following article, we present the rules and guidelines for gene nomenclature, and provide the current nomenclature for pigmentation mutants in the mouse.     

Cytokine milieu of atopic dermatitis,as compared to psoriasis,skin prevents induction of innate immune response genes

Atopic dermatitis (AD) and psoriasis are the two most common chronic skin diseases. However patients with AD, but not psoriasis, suffer from frequent skin infections. To understand the molecular basis for this phenomenon, skin biopsies from AD and psoriasis patients were analyzed using GeneChip microarrays. The expression of innate immune response genes, human beta defensin (HBD)-2, IL-8, and inducible NO synthetase (iNOS) was found to be decreased in AD, as compared with psoriasis, skin (HBD-2, p = 0.00021; IL-8, p = 0.044; iNOS, p = 0.016). Decreased expression of the novel antimicrobial peptide, HBD-3, was demonstrated at the mRNA level by real-time PCR (p = 0.0002) and at the protein level by immunohistochemistry (p = 0.0005). By real-time PCR, our data confirmed that AD, as compared with psoriasis, is associated with elevated skin production of Th2 cytokines and low levels of proinflammatory cytokines such as TNF-alpha, IFN-gamma, and IL-1beta. Because HBD-2, IL-8, and iNOS are known to be inhibited by Th2 cytokines, we examined the effects of IL-4 and IL-13 on HBD-3 expression in keratinocyte culture in vitro. We found that IL-13 and IL-4 inhibited TNF-alpha- and IFN-gamma-induced HBD-3 production. These studies indicate that decreased expression of a constellation of antimicrobial genes occurs as the result of local up-regulation of Th2 cytokines and the lack of elevated amounts of TNF-alpha and IFN-gamma under inflammatory conditions in AD skin. These observations could explain the increased susceptibility of AD skin to microorganisms, and suggest a new fundamental rule that may explain the mechanism for frequent infection in other Th2 cytokine-mediated diseases.     

Expression and significance of SOX B1 genes in glioblastoma multiforme patients

The overall survival of glioblastoma multiforme (GBM) patients remains poor. To improve patient outcomes, effective diagnostic and prognostic biomarkers for GBM are needed. In this study, we first applied bioinformatic analyses to identify biomarkers for GBM, focusing on SOX (sex‐determining region on the Y chromosome (SRY)‐related high mobility group (HMG) box) B1 family members. The ONCOMINE, GEPIA, LinkedOmics and CCLE databases were used to assess mRNA expression levels of the SOX B1 family members in different cancers and normal tissue. Further bioinformatic analysis was performed using the ONCOMINE database in combination with the LinkedOmics data set to identify the prognostic value of SOX B1 family members for GBM. We found mRNA expression levels of all tested SOX B1 genes were significantly increased in GBM. In the LinkedOmics database, increased expression of SOX3 indicated a better overall survival. In GEPIA databases, increased expression of all SOX B1 family members suggested an improved overall survival, but none of them were statistically different. Then, Transwell assays and wound healing were employed to evaluate the motility and invasive captivity of U251 cells when silencing SOX2 and SOX3. We found exogenous inhibition of SOX2 appeared to reduce the migration and invasion of U251 cells in vitro. Collectively, our research suggested that SOX2 might serve as a cancer‐promoting gene to identify high‐risk GBM patients, and SOX3 had the potential to be a prognostic biomarker for GBM patients.     

Expression of genes encoding antimicrobial and bradykinin-related peptides in skin of the stream brown frog Rana sakuraii

Peptidomic analysis of an extract of the skin of the stream brown frog Rana sakuraii Matsui and Matsui, 1990 led to the isolation of a C-terminally alpha-amidated peptide (VR-23; VIGSILGALASGLPTLISWIKNR x NH2) with broad-spectrum antimicrobial activity that shows structural similarity to the bee venom peptide, melittin together with two peptides belonging to the temporin family (temporin-1SKa; FLPVILPVIGKLLNGIL x NH2 and temporin-1SKb; FLPVILPVIGKLLSGIL x NH2), and peptides whose primary structures identified them as belonging to the brevinin-2 (2 peptides) and ranatuerin-2 (1 peptide) families. Using a forward primer that was designed from a conserved region of the 5'-untranslated regions of Rana temporaria preprotemporins in a 3'-RACE procedure, a cDNA clone encoding preprotemporin-1SKa was prepared from R. sakuraii skin total RNA. Further preprotemporin cDNAs encoding temporin-1SKc (AVDLAKIANIAN KVLSSL F x NH2) and temporin-1SKd (FLPMLAKLLSGFL x NH2) were obtained by RT-PCR. Unexpectedly, the 3'-RACE procedure using the same primer led to amplification of a cDNA encoding a preprobradykinin whose signal peptide region was identical to that of preprotemporin-1SKa except for the substitution Ser18-->Asn. R. sakuraii bradykinin ([Arg0,Leu1,Thr6,Trp8] BK) was 28-fold less potent than mammalian BK in effecting B2 receptor-mediated relaxation of mouse trachea and the des[Arg0] derivative was only a weak partial agonist. The evolutionary history of the Japanese brown frogs is incompletely understood but a comparison of the primary structures of the R. sakuraii dermal peptides with those of Tago's brown frog Rana tagoi provides evidence for a close phylogenetic relationship between these species.