Increased serum soluble vascular endothelial cadherin levels in patients with chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disease characterized by recurrent itchy wheals with or without angioedema that lasts longer than 6 weeks. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule that plays critical roles in angiogenesis and endothelial permeability. OBJECTIVE: To investigate serum levels of soluble VE (sVE)-cadherin in patients with CSU. METHODS: Serum levels of sVE-cadherin in patients with CSU, patients with atopic dermatitis, and healthy controls were determined by enzyme-linked immunosorbent assay. In addition, changes in sVE-cadherin serum levels were compared in patients with CSU before and after H1 antihistamine treatment. Furthermore, the effects of histamine on sVE-cadherin release by HMEC-1 cells were determined by enzyme-linked immunosorbent assay. The inhibition effects of H1 antihistamine and H2 antihistamine on sVE-cadherin release, VE-cadherin phosphorylation, and VE-cadherin disruption were evaluated in histamine-treated HMEC-1 cells by western blot and immunofluorescence. RESULTS: Serum levels of sVE-cadherin in patients with CSU were significantly higher than those in patients with atopic dermatitis and healthy controls. Serum sVE-cadherin levels in patients with CSU were correlated with the severity of CSU according to Urticaria Activity Scores. Furthermore, serum sVE-cadherin levels in patients with CSU at pretreatment decreased after H1 antihistamine treatment. In addition, histamine markedly induced sVE-cadherin release in HMEC-1 cells. Moreover, H1 antihistamine, but not H2 antihistamine, significantly inhibited sVE-cadherin release in histamine-treated HMEC-1 cells. Western blot data showed that histamine induced phosphorylation of VE-cadherin in HMEC-1 cells, which was blocked by H1 antihistamine. CONCLUSION: The present data showed serum levels of sVE-cadherin are increased in patients with CSU. Histamine-induced sVE-cadherin release from endothelial cells could play a role in the pathogenesis of CSU.

Paeoniflorin suppresses inflammatory response in imiquimod-induced psoriasis-like mice and peripheral blood mononuclear cells (PBMCs) from psoriasis patients.

Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders, characterized by hyperproliferation of keratinocytes, dilation and growth of dermal capillary vasculature, and cellular infiltration of T cells, dendritic cells (DCs), and neutrophils. Paeoniflorin (PF), the principal component of total glucosides of paeony (TGP), displays anti-inflammatory and antioxidant properties in several animal models. In this study, we investigated the anti-inflammatory effects and mechanisms of PF in imiquimod (IMQ)-induced psoriasis-like mouse model. The effects of PF on inflammatory cytokine expression in peripheral blood mononuclear cells (PBMCs) from patients with psoriasis vulgaris were also observed. Our results indicated that PF effectively attenuated the clinical and histopathologic changes in IMQ-induced psoriasis-like mouse model. Furthermore, PF reduced the infiltration of T cells, CD11c(+)DCs, and neutrophils in lesional skin. In addition, PF also significantly decreased the mRNA expression of inflammatory cytokines, such as IL-17, INF-γ, IL-6, and TNF-α, in IMQ-induced psoriasis-like mouse model and PBMCs from patients with psoriasis vulgaris. Hence, our data suggest that PF can inhibit leukocyte infiltration and decrease the expression of inflammatory cytokines such as IL-17, INF-γ, IL-6, and TNF-α. PF might be a candidate drug for the treatment of psoriasis.

Interleukin-35 inhibited the production of histamine and pro-inflammatory cytokines through suppression MAPKs pathway in HMC-1 cells.

BACKGROUND: IL-35 is a newly anti-inflammatory cytokine that belongs to the IL-12 family. Mast cells, as one of the major effector cells in the immune response system, plays an important role in the pathogenesis of chronic spontaneous urticarial (CSU). Our study aims to explore the inhibited role of IL-35 in HMC-1. METHODS: The effects of IL-35 on cell proliferation, cytokine expression, and histamine release in a human mast cell line (HMC-1) were investigated by CCK8, ELISA, or RT-PCR. The phosphorylation levels of ERK1/2, p38, and JNK1/2, in PMA plus A23187 induced HMC-1 cells was detected by Western Blot. RESULTS: We found that IL-35 significantly inhibited the proliferation of HMC-1 cells stimulated by PMA and A23187. IL-35 also down-regulates the release of histamine and the mRNA expression of IL-6 and IL-17 in activated HMC-1. Furthermore, IL-35 markedly inhibited the phosphorylation levels of ERK1/2, p38, and JNK1/2, in PMA plus A23187 induced HMC-1 cells. CONCLUSIONS: This study provides the first observations on the inhibitory and anti-inflammatory effect of IL-35 in activated HMC-1 cells. We suggest that IL35 may play an inhibited role in the pathogenesis of CSU.

Enhanced serum interferon-lambda 1 interleukin-29 levels in patients with psoriasis vulgaris.

BACKGROUND: Interferon (IFN)-λ1, also named Interleukin (IL)-29, is a new member of the Type III IFN or IFN-λ family. IL-29 plays an important role in the pathogenesis of many types of autoimmune and inflammatory diseases. OBJECTIVE: To study the role of IL-29 in the pathogenesis of psoriasis vulgaris. METHODS: The authors detected the serum levels of IL-29 in forty-one patients with psoriasis vulgaris, twenty-three patients with atopic dermatitis and thirty-eight age and gender-matched controls by sandwich Enzyme-Linked Immunosorbent Assay (ELISA). The effects of IL-29 on the expression of cytokines, such as IL-6, IL-17, IL-8, IL-4, IL10, Interferon (IFN-γ) and Tumor Necrosis Factor-α (TNF-α), in PBMCs and HaCat cells were determined by real-time quantitative PCR. RESULTS: Our data indicated that serum IL-29 levels were significantly elevated in patients with psoriasis vulgaris when compared with atopic dermatitis patients and the control group. Moreover, Serum levels of IL-29 were closely associated with the severity of psoriasis vulgaris. Furthermore, IL-29 up-regulated the mRNA expression levels of IL-6, IL-17 and TNF-α in PBMCs from psoriasis vulgaris patients. In addition, IL-29 enhanced the IL-6 and IL-8 expression from the HaCat cells. CONCLUSION: This study provides the first observations on the association of IL-29 and psoriasis vulgaris and showed elevated IL-29 serum levels. The authors suggest that IL-29 may play a role in the pathogenesis of psoriasis vulgaris.

Enhanced serum interferon-lambda 1/interleukin-29 levels in patients with psoriasis vulgaris

Abstract Background: Interferon (IFN)-λ1, also named Interleukin (IL)-29, is a new member of the Type III IFN or IFN-λ family. IL-29 plays an important role in the pathogenesis of many types of autoimmune and inflammatory diseases. Objective: To study the role of IL-29 in the pathogenesis of psoriasis vulgaris. Methods: The authors detected the serum levels of IL-29 in forty-one patients with psoriasis vulgaris, twenty-three patients with atopic dermatitis and thirty-eight age and gender-matched controls by sandwich Enzyme-Linked Immunosorbent Assay (ELISA). The effects of IL-29 on the expression of cytokines, such as IL-6, IL-17, IL-8, IL-4, IL10, Interferon (IFN-γ) and Tumor Necrosis Factor-α (TNF-α), in PBMCs and HaCat cells were determined by real-time quantitative PCR. Results: Our data indicated that serum IL-29 levels were significantly elevated in patients with psoriasis vulgaris when compared with atopic dermatitis patients and the control group. Moreover, Serum levels of IL-29 were closely associated with the severity of psoriasis vulgaris. Furthermore, IL-29 up-regulated the mRNA expression levels of IL-6, IL-17 and TNF-α in PBMCs from psoriasis vulgaris patients. In addition, IL-29 enhanced the IL-6 and IL-8 expression from the HaCat cells. Conclusion: This study provides the first observations on the association of IL-29 and psoriasis vulgaris and showed elevated IL-29 serum levels. The authors suggest that IL-29 may play a role in the pathogenesis of psoriasis vulgaris.

Elevated urinary levels of cystatin C and neutrophil gelatinase-associated lipocalin in Henoch-Schönlein purpura patients with renal involvement.

Henoch-Schönlein purpura (HSP) is a commonest systemic vasculitis in childhood. The long-term prognosis of HSP is determined by the degree of renal involvement. The aim of this study is to search novel clinically applicable biomarkers to evaluate renal involvement in HSP patients. 20 bio-indexes in urine samples were simultaneously screened by antibody array assay. We indicated that urinary levels of cystatin C (Cys C) and neutrophil gelatinase-associated lipocalin (NGAL) in HSP patients with renal involvement were significantly higher than those without renal involvement and healthy controls. Furthermore, ELISA was used to analyze urinary Cys C and NGAL levels in HSP patients with or without renal involvement, atopic dermatitis (AD) patients and healthy controls. Our results demonstrated that urinary Cys C and NGAL levels in HSP patients with renal involvement were significantly elevated, when compared with those without renal involvement, AD patients and control subjects. In addition, by receiver operating characteristic (ROC) curve analysis, we demonstrated that the area under the ROC curve of NGAL (0.789) was larger than that of Cys C (0.692). Taken together, we show firstly that urinary Cys C and NGAL levels is abnormally elevated in HSP patients with renal involvement. We suggest that urinary Cys C and NGAL are novel useful biomarkers of renal involvement in HSP patients.