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ABSTRACT: Psoriasis is an inflammatory cutaneous disorder characterized by marked epidermal thickening and Th1 and Th17 cell infiltration. At present, the contribution of B cells to the pathogenesis of psoriasis is unclear. In mice, topical application of imiquimod induces inflamed skin lesions and serves as an experimental animal model for human psoriasis. In this study, we showed that imiquimod-induced skin inflammation was more severe in CD19(-/-) than WT mice. These inflammatory responses were negatively regulated by a unique IL-10-producing CD1d(hi)CD5(+) regulatory B cell subset (B10 cells) that was absent in CD19(-/-) mice and represented only 1-2% of splenic B220(+) cells in WT mice. Splenic B10 cells entered the circulation and migrated to draining LNs during imiquimod-induced skin inflammation, thereby suppressing IFN-γ and IL-17 production. Furthermore, adoptive transfer of these B10 cells from WT mice reduced inflammation in CD19(-/-) mice. The present findings provide direct evidence that B10 cells regulate imiquimod-induced skin inflammation and offer insights into regulatory B cell-based therapies for the treatment of psoriasis.
Journal of leukocyte biology 04/2013; · 4.99 Impact Factor
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ABSTRACT: Atopic dermatitis is an inflammatory cutaneous disorder characterized by dry skin and relapsing eczematous skin lesions. Besides antibody production, the contribution of B cells to the pathogenesis of atopic dermatitis is unclear. In mice, repeated epicutaneous sensitization with ovalbumin induces inflamed skin lesions resembling human atopic dermatitis and therefore serves as an experimental model for this condition. To investigate the role of B cells in a murine model of atopic dermatitis, ovalbumin-sensitized allergic skin inflammation was assessed in mice lacking CD19. In ovalbumin-sensitized skin from CD19-deficient mice, the number of eosinophils and CD4(+) T cells was reduced, and both epidermal and dermal thickening were decreased. Following in vitro stimulation with ovalbumin, CD19 deficiency significantly reduced the proliferation of CD4(+), but not CD8(+), T cells from spleen and draining lymph nodes. Furthermore, splenocytes and draining lymph node cells from ovalbumin-sensitized CD19-deficient mice secreted significantly less IL-4, IL-13, and IL-17 than ovalbumin-sensitized wild-type mice. These results suggest that CD19 expression in B cells plays a critical role in antigen-specific CD4(+) T-cell proliferation and T helper 2 and 17 responses in a murine model of atopic dermatitis. Furthermore, the present findings may have implications for B-cell-targeted therapies for the treatment of atopic dermatitis.
American Journal Of Pathology 04/2013; · 4.89 Impact Factor
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Kaname Akamata,
Yoshihide Asano,
Shinji Noda,
Takashi Taniguchi,
Takehiro Takahashi,
Yohei Ichimura,
Tetsuo Toyama,
Hayakazu Sumida,
Yoshihiro Kuwano,
Koichi Yanaba, Yayoi Tada,
Makoto Sugaya,
Takafumi Kadono,
Shinichi Sato
European journal of dermatology : EJD. 04/2013;
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ABSTRACT: CXCR4 is expressed by basal keratinocytes (KCs), but little is known about its function in inflamed skin. We crossed K14-Cre and CXCR4(flox/flox (f/f)) transgenic mice, resulting in mice with specific loss of the CXCR4 gene in K14-expressing cells (K14-CXCR4KO), including basal KCs. K14-CXCR4KO pups had no obvious skin defects. We compared K14-CXCR4KO and CXCR4(f/f) control mice in an IL-23-mediated psoriasisform dermatitis model and measured skin edema, histologic, and immunohistological changes. IL-23-treated K14-CXCR4KO mice showed a 1.3-fold increase in mean ear swelling, 2-fold increase in epidermal thickness, and greater parakeratosis. IL-23-treated WT mice showed weak CXCR4 expression in areas of severe epidermal hyperplasia, but strong CXCR4 expression in non-hyperplastic regions, suggesting CXCR4 may regulate keratinocyte proliferation. To test this hypothesis, we overexpressed CXCR4 in HaCaT keratinocyte cells and treated them with IL-22 and/or CXCL12. CXCL12 blocked IL-22-mediated HaCaT cell proliferation in vitro and synergized with IL-22 in upregulating SOCS3, a key regulator of STAT3. SOCS3 was required for CXCR4-mediated growth inhibition. In human psoriatic skin, both CXCR4 and SOCS3 were upregulated in the junctional region at the border of psoriatic plaques. Thus, CXCR4 plays an unexpected role in inhibiting KC proliferation and mitigating the effects of proliferative Th17 cytokines.Journal of Investigative Dermatology accepted article preview online, 25 March 2013; doi:10.1038/jid.2013.151.
Journal of Investigative Dermatology 03/2013; · 6.31 Impact Factor
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ABSTRACT: Psoriasis, a chronic inflammatory dermatosis, is frequently associated with metabolic disorders, suggesting that adipokines are involved in its pathogenesis. We recently reported that the adipokine visfatin activates NF-κB and STAT3 in keratinocytes. Antimicrobial peptide expression is enhanced in psoriatic lesions and may promote disease development. Here, we investigated the effects of visfatin on antimicrobial peptide expression. In vitro, visfatin enhanced basal and tumor necrosis factor-α (TNF-α)-induced mRNA expression and secretion of cathelicidin antimicrobial peptide (CAMP), and enhanced TNF-α-induced human β-defensin-2 (hBD-2), hBD-3, and S100A7 mRNA expression and secretion in human keratinocytes. siRNAs targeting CCAAT/enhancer-binding protein-α (C/EBPα) suppressed visfatin-induced and visfatin plus TNF-α-induced CAMP production. siRNAs targeting NF-κB p65 and STAT3 suppressed visfatin plus TNF-α-induced hBD-2 and S100A7 production. siRNAs targeting c-Jun and STAT3 suppressed visfatin plus TNF-α-induced hBD-3 production. Visfatin and/or TNF-α enhanced C/EBP transcriptional activity and C/EBPα phosphorylation, which were suppressed by p38 mitogen-activated protein kinase (MAPK) inhibition. Visfatin and/or TNF-α induced p38 MAPK phosphorylation. Visfatin increased mRNA and protein expression of CAMP, hBD-2, hBD-3, and S100A7 orthologs in murine imiquimod-treated skin, mimicking psoriasis. In conclusion, visfatin enhances CAMP, hBD-2, hBD-3, and S100A7 production in human keratinocytes and their orthologs in murine imiquimod-treated psoriatic skin. Visfatin may potentiate the development of psoriasis via antimicrobial peptides.
American Journal Of Pathology 03/2013; · 4.89 Impact Factor
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Yuri Masui,
Yoshihide Asano,
Sayaka Shibata,
Shinji Noda,
Kaname Akamata,
Naohiko Aozasa,
Takashi Taniguchi,
Takehiro Takahashi,
Yohei Ichimura,
Tetsuo Toyama,
Hayakazu Sumida,
Koichi Yanaba, Yayoi Tada,
Makoto Sugaya,
Shinichi Sato,
Takafumi Kadono
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ABSTRACT: Objective. Visfatin is a member of the adipocytokines with pro-fibrotic, pro-inflammatory and immunomodulating properties potentially implicated in the pathogenesis of certain fibrotic and inflammatory autoimmune diseases. In this study, we investigated the clinical significance of serum visfatin levels and its contribution to the developmental process in SSc.Methods. Serum visfatin levels were determined by a specific ELISA in 57 SSc patients and 19 healthy controls. The mRNA levels of target genes were determined in normal and SSc fibroblasts by real-time RT-PCR. The levels of IL-12p70 produced by THP-1 cells were measured by a specific ELISA.Results. Serum visfatin levels were comparable among total SSc, diffuse cutaneous SSc (dcSSc), limited cutaneous SSc and healthy controls. The only finding in a series of analyses regarding the correlation of serum visfatin levels with clinical symptoms and laboratory data was the significantly longer disease duration in dcSSc with elevated serum visfatin levels than in those with normal levels. Consistently, serum visfatin levels were significantly elevated in late-stage dcSSc (disease duration >6 years), but not in early and mid-stage dcSSc compared with healthy controls. In in vitro experiments, visfatin reversed the pro-fibrotic phenotype of SSc dermal fibroblasts and induced the expression of IL-12p70 in THP-1 cells treated with IFN-γ plus lipopolysaccharide.Conclusion. Visfatin may contribute to the resolution of skin sclerosis in late-stage dcSSc via a direct anti-fibrotic effect on dermal fibroblasts and Th1 polarization of the immune response.
Rheumatology (Oxford, England) 02/2013; · 4.24 Impact Factor
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Acta Dermato-Venereologica 01/2013;
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Shinji Noda,
Yoshihide Asano,
Takehiro Takahashi,
Kaname Akamata,
Naohiko Aozasa,
Takashi Taniguchi,
Yohei Ichimura,
Tetsuo Toyama,
Hayakazu Sumida,
Yoshihiro Kuwano,
Koichi Yanaba, Yayoi Tada,
Makoto Sugaya,
Takafumi Kadono,
Shinichi Sato
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ABSTRACT: Objectives. Cathepsin V (CTSV) is a proteolytic enzyme potentially modulating angiogenic processes, collagen degradation and keratinocyte differentiation. We aimed to investigate the clinical association of serum CTSV levels and the mechanism by which CTSV expression is altered in SSc.Methods. Serum CTSV levels were determined by ELISA in 51 SSc and 18 healthy subjects. CTSV expression was evaluated by immunostaining in SSc and normal skin and by RT-real-time PCR in normal and SSc dermal fibroblasts, normal dermal fibroblasts treated with TGF-β1 or Fli1 siRNA and human dermal microvascular endothelial cells (ECs) treated with Fli1 siRNA.Results. Serum CTSV levels were significantly lower in dcSSc and lcSSc patients than in healthy controls. In early-stage dcSSc, serum CTSV levels were remarkably and uniformly decreased compared with healthy controls. The decrease in serum CTSV levels in mid- and late-stage dcSSc and in lcSSc was linked to the development of proliferative vasculopathy. CTSV expression was decreased in microvascular ECs, pericytes/vascular smooth muscle cells and keratinocytes of dcSSc and lcSSc skin and in dermal fibroblasts of dcSSc skin compared with control skin. Consistently, CTSV expression was decreased in cultured dermal fibroblasts from early-stage dcSSc. Furthermore, mRNA levels of the CTSV gene were significantly decreased in normal fibroblasts treated with TGF-β1 or Fli1 siRNA and in human dermal microvascular ECs treated with Fli1 siRNA.Conclusion. Loss of CTSV expression may contribute to the development of fibrosis, vasculopathy and the altered phenotype of keratinocytes in SSc.
Rheumatology (Oxford, England) 01/2013; · 4.24 Impact Factor
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Shinji Noda,
Yoshihide Asano,
Naohiko Aozasa,
Kaname Akamata,
Takashi Taniguchi,
Takehiro Takahashi,
Yohei Ichimura,
Tetsuo Toyama,
Hayakazu Sumida,
Yoshihiro Kuwano,
Koichi Yanaba, Yayoi Tada,
Makoto Sugaya,
Takafumi Kadono,
Shinichi Sato
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ABSTRACT: Tie1 is an endothelial cell-specific tyrosine kinase receptor, which maintains vascular integrity and regulates angiogenesis via modulating angiopoietin/Tie2 signaling. Since the altered angiogenesis is closely related to the developmental process of systemic sclerosis (SSc), we herein investigated the clinical significance of serum soluble Tie1 (sTie1) levels and the expression levels of Tie1 in dermal microvascular endothelial cells (DMECs) in patients with SSc. Although serum sTie1 levels were comparable among total SSc, diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and healthy controls, SSc patients with decreased serum sTie1 levels had significantly shorter disease duration than those with serum sTie1 levels not decreased. In SSc patients with disease duration of >6 years, the prevalence of clinical symptoms associated with proliferative vasculopathy, such as digital ulcers, scleroderma renal crisis, and elevated right ventricular systolic pressure, was significantly higher in patients with decreased serum sTie1 levels than in those with serum sTie1 levels not decreased. In immunohistochemistry, Tie1 expression was reduced in DMECs of SSc patients with disease duration of <3 years compared with those of healthy controls. Collectively, in SSc patients with short disease duration, decreased serum sTie1 levels may reflect the down-regulation of Tie1 in DMECs. The decrease in serum sTie1 levels may serve as a marker of proliferative vasculopathy in SSc with disease duration of >6 years.
Archives for Dermatological Research 12/2012; · 2.28 Impact Factor
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Koichi Yanaba,
Yoshihide Asano,
Shinji Noda,
Kaname Akamata,
Naohiko Aozasa,
Takashi Taniguchi,
Takehiro Takahashi,
Yohei Ichimura,
Tetsuo Toyama,
Hayakazu Sumida,
Yoshihiro Kuwano, Yayoi Tada,
Makoto Sugaya,
Takafumi Kadono,
Shinichi Sato
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ABSTRACT: Inducible costimulator (ICOS) is crucial for T cell proliferation, production of various cytokines, and T cell-dependent B-cell responses. To determine the serum soluble ICOS (sICOS) level and its association with clinical parameters in patients with systemic sclerosis (SSc), serum sICOS level was examined by enzyme-linked immunosorbent assay in 38 patients with SSc and 24 healthy individuals. The expression of ICOS and ICOS ligand in skin was examined immunohistochemically. There was no significant difference in serum sICOS level between patients with SSc and healthy individuals. Patients with diffuse cutaneous SSc had higher levels of sICOS than those with limited cutaneous SSc (P < 0.05) or healthy individuals (P < 0.05). Serum sICOS level correlated positively with the severity of skin sclerosis. Patients with SSc and elevated sICOS level more often had interstitial lung disease and decreased vital capacity than those with normal sICOS level. The serum sICOS level was significantly greater in patients with early phase SSc than those with late phase SSc. ICOS and ICOS ligand immunostaining were observed on infiltrating dermal mononuclear cells in lesional skin tissue. These results suggest that the serum level of sICOS is increased in patients with diffuse cutaneous SSc and correlates with the severity and activity of skin sclerosis and interstitial lung disease. ICOS may contribute to the development of SSc. In addition, measurement of serum sICOS level in patients with early SSc may offer an important means for further evaluation of SSc disease severity.
Archives for Dermatological Research 10/2012; · 2.28 Impact Factor
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Koichi Yanaba,
Yoshihide Asano,
Shinji Noda,
Kaname Akamata,
Naohiko Aozasa,
Takashi Taniguchi,
Takehiro Takahashi,
Yohei Ichimura,
Tetsuo Toyama,
Hayakazu Sumida,
Yoshihiro Kuwano, Yayoi Tada,
Makoto Sugaya,
Takafumi Kadono,
Shinichi Sato
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ABSTRACT: Fibrinogen-like protein 2 (FGL2), a member of the fibrinogen-related superfamily of proteins, is expressed on the surface of macrophages, T cells, and endothelial cells and directly cleaves prothrombin to thrombin. The aim of this study is to determine the serum FGL2 level and its association with clinical parameters in patients with systemic sclerosis (SSc). Serum FGL2 level was examined by enzyme-linked immunosorbent assay in 61 patients with SSc, 24 patients with systemic lupus erythematosus, and 24 healthy individuals. In a retrospective longitudinal study, sera from 13 patients with SSc were analyzed. The serum FGL2 level was increased in patients with SSc compared with healthy individuals (P < 0.001) and patients with systemic lupus erythematosus (P < 0.01). Among patients with SSc, there were no differences in serum FGL2 level between limited cutaneous SSc and diffuse cutaneous SSc. In the longitudinal study, the FGL2 level was generally unchanged at follow-up. The results show that the serum FGL2 level was increased in patients with SSc but not in patients with systemic lupus erythematosus or healthy individuals. Therefore, FGL2 possibly contribute to the development of SSc.
Clinical Rheumatology 09/2012; · 2.00 Impact Factor
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Takehiro Takahashi,
Yoshihide Asano,
Kaname Akamata,
Naohiko Aozasa,
Takashi Taniguchi,
Shinji Noda,
Yuri Masui,
Yohei Ichimura,
Tetsuo Toyama,
Zenshiro Tamaki, Yayoi Tada,
Makoto Sugaya,
Takafumi Kadono,
Shinichi Sato
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ABSTRACT: OBJECTIVE: Angiopoietin-2 (Ang2) regulates the transition between vascular quiescence and angiogenesis in a context-dependent manner. In systemic sclerosis (SSc), serum Ang2 levels correlate with its disease activity. Therefore, we investigated the clinical significance of monitoring serum Ang2 levels during intravenous pulse cyclophosphamide (IVCY) therapy in SSc patients with interstitial lung disease (ILD). METHODS: Serum Ang2 levels were determined by a specific enzyme-linked immunosorbent assay in seven SSc patients treated with IVCY and 20 healthy controls. In the patient group, serum samples were drawn the day before each IVCY therapy. RESULTS: Serum Ang2 levels tended to be higher in SSc patients before IVCY than in healthy controls and significantly correlated with KL-6, surfactant protein D, erythrocyte sedimentation rate, and C-reactive protein in SSc patients with ILD. In sera drawn before the last IVCY, Ang2 levels were significantly decreased compared with initial levels. Notably, Δ serum Ang2 levels between baseline and after the first IVCY significantly correlated with Δ ILD score between before and after the entire IVCY therapy (r = 0.90, p < 0.01). CONCLUSION: Monitoring Ang2 levels during IVCY treatment may be useful to evaluate and predict the efficacy of this treatment for SSc-ILD.
Modern Rheumatology 09/2012; · 1.58 Impact Factor
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ABSTRACT: IL-27, a member of the IL-12 cytokine family, primes Th1 cell differentiation, whereas it suppresses Th17 cell development. We have previously reported that serum IL-27 levels are elevated in psoriatic patients and that IL-27 greatly induces in vitro production of Th1-type chemokines through STAT1 activation. In this study, to further investigate the in vivo role of IL-27 in the pathogenesis of psoriasis, we induced psoriasis-like inflammation on mouse back skin with topical application of imiquimod (IMQ), and continuously injected IL-27 or PBS subcutaneously. IMQ-treated skin showed an increase of IL-27 mRNA levels and the infiltration of IL-27-producing cells in the papillary dermis. The injection of IL-27 to the IMQ-treated skin exacerbated the disease compared with PBS injection. The IL-27 injection further augmented mRNA levels of IFN-γ, CXCL9, CXCL10, CXCL11, and TNF-α, without altering those of IL-17A, IL-17F, IL-22, and CCL20. Finally, IL-27 antagonism attenuated the upregulation of IFN-γ, CXCL9, CXCL10, CXCL11, and TNF-α mRNA levels, and induced clinical and histological improvement in the IMQ-treated skin. These results indicate that IL-27 would act in a proinflammatory manner, and thereby exacerbate the psoriasis-like skin inflammation induced by IMQ.Journal of Investigative Dermatology advance online publication, 6 September 2012; doi:10.1038/jid.2012.313.
Journal of Investigative Dermatology 09/2012; · 6.31 Impact Factor
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ABSTRACT: Many patients with cutaneous T-cell lymphoma (CTCL) experience severe pruritus. This study evaluated serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in patients with CTCL. Although serum NGF and BDNF levels in patients with CTCL were not significantly higher than in healthy controls, serum NGF levels in patients with Sézary syndrome were higher than in those with mycosis fungoides and in healthy controls. Enhanced NGF expression by keratinocytes and increased dermal nerve fibres were detected in lesional skin of subjects with Sézary syndrome. Correlations between pruritus in CTCL and serum levels of NGF, BDNF, chemokine (C-C motif) ligand 1 (CCL1), CCL17, CCL26, CCL27, lactate dehydrogenase (LDH), IgE, and soluble interleukin-2 receptor were analysed. Serum CCL1, CCL26, LDH, and IgE levels correlated with pruritus in patients with CTCL. NGF may be associated with increased dermal nerve fibres and pruritus in Sézary syndrome, and CCL1, CCL26, and IgE may be associated with pruritus in CTCL.
Acta Dermato-Venereologica 09/2012;
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ABSTRACT: Diabetic patients are at high risk of developing delayed cutaneous wound healing. Adiponectin plays a pivotal role in the pathogenesis of diabetes and is considered to be involved in various pathological conditions associated with diabetes; however, its role in wound repair is unknown. In this study, we elucidated the involvement of adiponectin in cutaneous wound healing in vitro and in vivo. Normal human keratinocytes expressed adiponectin receptors, and adiponectin enhanced proliferation and migration of keratinocytes in vitro. This proliferative and migratory effect of adiponectin was mediated via AdipoR1/AdipoR2 and the ERK signaling pathway. Consistent with in vitro results, wound closure was significantly delayed in adiponectin-deficient mice compared with wild-type mice, and more importantly, keratinocyte proliferation and migration during wound repair were also impaired in adiponectin-deficient mice. Furthermore, both systemic and topical administration of adiponectin ameliorated impaired wound healing in adiponectin-deficient and diabetic db/db mice, respectively. Collectively, these results indicate that adiponectin is a potent mediator in the regulation of cutaneous wound healing. We propose that upregulation of systemic and/or local adiponectin levels is a potential and very promising therapeutic approach for dealing with diabetic wounds.
The Journal of Immunology 08/2012; 189(6):3231-41. · 5.79 Impact Factor
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Makoto Sugaya,
Tomomitsu Miyagaki,
Hanako Ohmatsu,
Hiraku Suga,
Hiromichi Kai,
Masahiro Kamata,
Hideki Fujita,
Yoshihide Asano, Yayoi Tada,
Takafumi Kadono,
Hitoshi Okochi,
Shinichi Sato
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ABSTRACT: Classically activated macrophages produce IL-12, IL-23, and TNF-α, whereas alternatively activated macrophages (M2 cells) produce IL-10 and express several receptors such as mannose receptor and CD163. Tumor-associated macrophages exhibit M2 phenotype, whose presence has been associated with poor prognosis in various tumors.
To investigate distribution of CD163(+) cells in lesional skin and serum levels of soluble CD163 (sCD163) in patients with cutaneous T cell lymphoma (CTCL), atopic dermatitis (AD), or psoriasis.
The numbers of CD163(+) and CD68(+) cells in lesional skin of CTCL, AD, or psoriasis, and in normal skin were examined by immunohistochemistry. Serum soluble CD163 (sCD163) levels were quantified by enzyme-linked immunosorbent assay.
The numbers of CD163(+) cells in lesional skin of CTCL, AD, or psoriasis were significantly larger than in normal skin. In CTCL, the numbers of CD163(+) or CD68(+) cells increased as more tumor cells infiltrated and they decreased after treatment with topical steroid and ultraviolet light. Moreover, CTCL patients with an increased number of CD163(+) cells showed worse prognosis. Serum sCD163 levels in patients with CTCL, AD, or psoriasis were significantly higher than those in normal controls. In CTCL patients, serum sCD163 levels significantly correlated with serum soluble interleukin-2 receptor and CCL17 levels. In AD patients, serum sCD163 levels correlated with serum IgE levels.
The numbers of CD163(+) cells in lesional skin and serum sCD163 levels were associated with disease progression of CTCL. Further study focusing on CD163(+) cells in CTCL lesional skin would be an interesting research field.
Journal of dermatological science 07/2012; 68(1):45-51. · 3.71 Impact Factor
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Yuri Masui,
Yoshihide Asano,
Takehiro Takahashi,
Sayaka Shibata,
Kaname Akamata,
Naohiko Aozasa,
Shinji Noda,
Takashi Taniguchi,
Yohei Ichimura,
Tetsuo Toyama,
Zenshiro Tamaki,
Hayakazu Sumida,
Koichi Yanaba, Yayoi Tada,
Makoto Sugaya,
Shinichi Sato,
Takafumi Kadono
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ABSTRACT: OBJECTIVE: To investigate the clinical significance of monitoring serum adiponectin levels during intravenous pulse cyclophosphamide (IVCY) in systemic sclerosis (SSc) patients with interstitial lung disease (ILD). METHODS: Serum adiponectin levels were determined by a specific enzyme-linked immunosorbent assay in eight SSc patients with active ILD who underwent IVCY and 27 healthy controls. In patients, serum samples were drawn the day before each IVCY. RESULTS: Serum adiponectin levels were significantly decreased in SSc patients with active ILD before the first IVCY compared with healthy controls [median (25-75 percentile): 3.21 (2.70-4.19) vs. 7.42 (6.06-10.82) μg/ml; P < 0.01). After the completion of whole IVCY, serum adiponectin levels were significantly increased [17.55 (6.47-39.45) μg/ml; P < 0.05] compared with the initial levels, and this increase significantly correlated with the decrease in ILD scores. Importantly, the dynamics of serum adiponectin levels during the IVCY therapy reflected its efficacy against SSc-ILD over the treatment and the follow-up period. CONCLUSION: The monitoring of serum adiponectin levels during the IVCY treatment may be useful to identify SSc patients with ILD refractory to the treatment and at high risk for exacerbations during the follow-up period.
Modern Rheumatology 05/2012; · 1.58 Impact Factor
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ABSTRACT: Angiogenin is a member of the ribonuclease superfamily that is associated with the angiogenic process. Angiogenesis is regarded as an important step to support primary and metastatic tumor growth. In cutaneous T cell lymphoma (CTCL), angiogenesis in lesional skin is increased, suggesting that interaction between tumor cells and their microvasculature are likely to occur during progression of CTCL. Patients with hematological malignancies show increased serum angiogenin levels, which are related with poor overall survival. To investigate possible roles of angiogenin in development of CTCL, we measured serum angiogenin levels in 36 patients with CTCL and 21 healthy controls by enzyme-linked immunosorbent assay. We also investigated angiogenin mRNA and protein expression in lesional skin of CTCL by quantitative RT-PCR and immunohistochemistry. Serum angiogenin levels in patients with CTCL were significantly higher than those in healthy controls. When classified with types of skin lesions, serum angiogenin levels were elevated only in erythrodermic CTCL patients. Angiogenin mRNA expression levels in lesional skin were significantly elevated in erythrodermic CTCL compared to normal skin. Immunohistochemical study revealed that angiogenin was expressed by keratinocytes, endothelial cells, and infiltrating lymphocytes in CTCL. Our results suggest that enhanced angiogenin expression may be related with a poor prognosis of erythrodermic CTCL. As angiogenin acts as an inhibitor of polymorphonuclear leukocyte degranulation, angiogenin may also be linked to impaired host defense in erythrodermic CTCL.
Archives for Dermatological Research 04/2012; 304(5):401-6. · 2.28 Impact Factor
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Hanako Ohmatsu,
Makoto Sugaya,
Hiraku Suga,
Sohshi Morimura,
Tomomitsu Miyagaki,
Hiromichi Kai,
Shinji Kagami,
Hideki Fujita,
Yoshihide Asano, Yayoi Tada,
Takafumi Kadono,
Shinichi Sato
Acta Dermato-Venereologica 03/2012; 92(3):282-3.
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Daisuke Yamada,
Yoshihide Asano,
Takehiro Takahashi,
Yuri Masui,
Naohiko Aozasa,
Kaname Akamata,
Shinji Noda,
Zenshiro Tamaki, Yayoi Tada,
Makoto Sugaya,
Shinichi Sato,
Takafumi Kadono
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ABSTRACT: Decoy receptor 3 (DcR3) is associated with autoimmunity and altered angiogenesis in certain pathological conditions. We herein measured serum DcR3 levels in 51 patients with systemic sclerosis (SSc) and 19 healthy controls and evaluated their clinical significance in this disorder. Serum DcR3 levels were significantly higher in diffuse cutaneous SSc (dcSSc) patients than in limited cutaneous SSc patients and in healthy controls. In dcSSc, serum DcR3 levels were significantly elevated in patients with disease duration of ≤6 years compared with healthy controls, but not in those with disease duration of >6 years. Serum DcR3 levels correlated negatively with the percentage of predicted diffusion lung capacity for carbon monoxide and positively with right ventricular systolic pressure. Furthermore, serum DcR3 levels positively correlated with C-reactive protein, erythrocyte sedimentation rate and immunoglobulin G. Collectively, the elevation of serum DcR3 levels is associated with the development of pulmonary arterial hypertension and systemic inflammation in SSc.
European journal of dermatology: EJD 03/2012; 22(3):351-7. · 2.53 Impact Factor
