Dimerized Translationally Controlled Tumor Protein-Binding Peptide Ameliorates Atopic Dermatitis in NC/Nga Mice.

Our previous study showed that dimerized translationally controlled tumor protein (dTCTP) plays a role in the pathogenesis of allergic diseases, such as asthma and allergic rhinitis. A 7-mer peptide, called dTCTP-binding peptide 2 (dTBP2), binds to dTCTP and inhibits its cytokine-like effects. We therefore examined the protective effects of dTBP2 in house dust mite-induced atopic dermatitis (AD)-like skin lesions in Nishiki-nezumi Cinnamon/Nagoya (NC/Nga) mice. We found that topical administration of dTBP2 significantly reduced the AD-like skin lesions formation and mast cell infiltration in NC/Nga mice, similarly to the response seen in the Protopic (tacrolimus)-treated group. Treatment with dTBP2 also decreased the serum levels of IgE and reduced IL-17A content in skin lesions and inhibited the expression of mRNAs of interleukin IL-4, IL-5, IL-6, IL-13, macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC) and thymic stromal lymphopoietin (TSLP). These findings indicate that dTBP2 not only inhibits the release of Th2 cytokine but also suppresses the production of proinflammatory cytokines in AD-like skin lesions in NC/Nga mice, by inhibiting TCTP dimer, in allergic responses. Therefore, dTCTP is a therapeutic target for AD and dTBP2 appears to have a potential role in the treatment of AD.

Potential of Translationally Controlled Tumor Protein-Derived Protein Transduction Domains as Antigen Carriers for Nasal Vaccine Delivery.

Nasal vaccination offers a promising alternative to intramuscular (i.m.) vaccination because it can induce both mucosal and systemic immunity. However, its major drawback is poor absorption of large antigens in the nasal epithelium. Protein transduction domains (PTDs), also called cell-penetrating peptides, have been proposed as vehicles for nasal delivery of therapeutic peptides and proteins. Here, we evaluated the potential of a mutant PTD derived from translationally controlled tumor protein (designated TCTP-PTD 13) as an antigen carrier for nasal vaccines. We first compared the l- and d-forms of TCTP-PTD 13 isomers (l- or d-TCTP-PTD 13) as antigen carriers. Studies in mice demonstrated that nasally administered mixtures of the model antigen ovalbumin (OVA) and d-TCTP-PTD 13 induced higher plasma IgG titers and secretory IgA levels in nasal washes than nasally administered OVA alone, OVA/l-TCTP-PTD 13, or i.m.-injected OVA. Plasma IgG subclass responses (IgG1 and IgG2a) of mice nasally administered OVA/d-TCTP-PTD 13 showed that the predominant IgG subclass was IgG1, indicating a Th2-biased immune response. We also used synthetic CpG oligonucleotides (CpG) as a Th1 immune response-inducing adjuvant. Nasally administered CpG plus OVA/d-TCTP-PTD 13 was superior in eliciting systemic and mucosal immune responses compared to those induced by nasally administered OVA/d-TCTP-PTD 13. Furthermore, the OVA/CpG/d-TCTP-PTD 13 combination skewed IgG1 and IgG2a profiles of humoral immune responses toward a Th1 profile. These findings suggest that TCTP-derived PTD is a suitable vehicle to efficiently carry antigens and to induce more powerful antigen-specific immune responses and a more balanced Th1/Th2 response when combined with a DNA adjuvant.

Red Seaweed-derived Compounds: A Desired Approach for Treating Cancer.

Cancer is a collection of diseases in which aberrant cells grow uncontrolled and invade surrounding tissues. Cancer can be classified as carcinoma, sarcoma, leukemia, or lymphoma. The deadliest cancers are lung, breast, colorectal, pancreatic, and prostate. Chemotherapy, surgery, and radiotherapy are the usual cancer treatments. However, drug resistance poses a significant barrier to cancer treatment. Macroalgae are wellknown producers of bioactive compounds with antimicrobial, antioxidant, anti-inflammatory, and anti-cancer properties. Red algae, in particular, are a prominent source of bioactive substances, such as polysaccharides, phenolic compounds, lipids, sterols, alkaloids, and terpenoids. Therefore, molecules from marine resources could be an appealing way to identify new cancer treatment alternatives. This study aimed to provide a brief overview of what is currently known regarding the potential of red macroalgae in cancer treatment by discussing the primary therapeutic targets of the disease and identifying compounds or extracts with bioactive characteristics against them.

Expression Pattern and Role of Klotho in Human Hair Follicles.

BACKGROUND: Klotho protein plays a pivotal role in aging regulation. However, it is unclear whether klotho is expressed in human hair follicles and is correlated with hair growth. OBJECTIVE: The purpose of this study was to determine the expression pattern and role of klotho in human hair follicles. METHODS: We examined the klotho expression patterns in human hair follicles from young and aged donors. Furthermore, we examined the functional roles of klotho on human hair growth using klotho siRNA and klotho recombinant protein. RESULTS: Interestingly, klotho was expressed in human hair follicles at both gene and protein levels. In hair follicles, prominent klotho expression was mainly observed in the outermost regions of the outer root sheath and hair bulb matrix cells. Quantification of klotho protein expression in young and aged donors showed that klotho expression decreased with aging. In human hair follicle organ culture, klotho silencing promoted premature catagen induction and inhibited human hair growth. Otherwise, klotho protein prolonged human hair growth. CONCLUSION: These results indicate that klotho might be an important regulatory factor for human hair growth and hair cycle change.

Effects of calcitonin gene-related peptide on the immune privilege of human hair follicles.

The hair follicle is a widely available and instructive miniature organ in the human body that experiences major histocompatibility complex (MHC) class I dependent immune privilege (IP). There are various regulation factors that act on the generation, maintenance, and collapse of hair follicle IP. Neuropeptides such as calcitonin gene-related peptide (CGRP) are created in many organs, including skin, and display various immune regulation effects. The purpose of this study was to investigate the phenotypic effect of CGRP on the hair follicle's IP. First, we used interferon-γ (IFN-γ) to generate ectopic MHC antigen expression model in cultured human hair follicles as previously described. Then, we examined the effects of CGRP on the regulation of ectopic MHC antigen expression in cultured human hair follicles using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical staining techniques. IFN-γ (75 IU/ml) induced ectopic MHC expression. CGRP down-regulated INF-γ-induced ectopic MHC class I mRNA expression. These down-regulated effects were especially evident in 10(-8)M. In addition, CGRP also suppressed the staining intensity related to the expression of MHC class I and MHC class I-pathway related molecules (ß2-microglobulin), but had no effect on MHC class II antigen expression. Taken together, these results indicate that CGRP might be an important regulatory factor for IP maintenance and restoration of IP via suppression of MHC class I antigen.