Group B Streptococcus (GBS) has been increasingly associated with invasive disease in nonpregnant adults. Such infections are responsible for substantial morbidity and mortality, particularly in individuals with underlying chronic conditions.
Tight junctions (TJs) play important roles in epidermal barrier function and their dysfunction is involved in the pathogenesis of various skin diseases, including atopic dermatitis (AD). Mucopolysaccharide polysulphate (MPS) is the active ingredient of a moisturizing agent used to treat xerosis in patients with AD; however, its mechanism of action on TJ barrier function remains unclear. To elucidate the effects of MPS on TJs, adult human epidermal keratinocyte (HEKa) cells were exposed to MPS, subjected to Western blotting and quantitative PCR analyses for the investigation of TJ‐related factors. MPS treatment significantly increased the mRNA and protein expression of claudin‐1 (CLDN1) and zonula occludens‐1, and significantly increased transepithelial electrical resistance (TEER), which indicates TJ integrity. Conversely, the sulphated and non‐sulphated glycosaminoglycans, chondroitin sulphate and hyaluronic acid, respectively, had little effect on TEER or the expression of mRNAs or TJ‐related proteins. Interestingly, MPS treatment also inactivated the extracellular signal‐regulated kinase signalling pathway, which is known to negatively regulate CLDN1 expression. Furthermore, MPS notably improved the reduction in CLDN1 expression and TEER caused by histamine, which is upregulated in the skin of patients with AD and is known to disrupt the TJ barrier function. Taken together, these findings demonstrate that treatment with the moisturizing agent, MPS, can repair TJ dysfunction and could therefore represent a new therapeutic option for treating patients with AD.
Background: C3H/HeJ mouse models progress gradually in hair loss from acute to chronic phase and reflect the symptoms of patients with alopecia areata (AA). However, the underlying pathological characteristics alteration associated with disease progression and autoantigens remain unclear. Objective: We aimed at elucidating the pathological differences between acute and chronic-AA in the C3H/HeJ mouse model. Methods: We analyzed populations of PBMCs, skin-draining lymph node (SDLN) cells, and cutaneous cells of AA mice using flow cytometry. The cytokine and chemokine expressions in the serum and skin were determined using multiplex assay and qPCR. The antibody serum levels were determined using ELISA and the antigen-specific T cells were detected using the MHC class I tetramer. Results: The CD8 + NKG2D + T and CD8 + T EM cell percentage in the chronic-AA SDLNs or among the unaffected and acute-AA mice PBMCs increased. The Th1 and CD4 + T EM cell percentage in the SDLNs and among PBMCs increased in the unaffected and AA mice. The percentage of CD8 + T EM /T RM cells and MHC class I expression increased in the lesions of acute-AA or the non-lesions and lesions of chronic-AA. The Th1 cells, dendritic cell-related cytokines, CD11c + cells and MHC class II expression increased in the skin of AA mice. The antibody levels and TYRP2 and tyrosinase-specific CD8 + T cell percentages were upregulated in AA mice. Conclusion:These results suggest that the CD8 + and CD4 + T cell subpopulations, cytokine and chemokine expressions differ between the disease phases. Moreover, TYRP2 and tyrosinase are potential autoreactive targets in the AA mouse model.
Ozenoxacin is a topical quinolone showing potent antimicrobial activities against Gram-negative and Gram-positive bacteria and is widely used for the treatment of inflammatory acne. However, the anti-inflammatory activities of ozenoxacin have not been examined so far. In the present study, we investigated the in vitro and in vivo anti-inflammatory effects of ozenoxacin. The production of interleukin (IL)-6 and IL-8 by human epidermal keratinocytes stimulated by heat-killed Cutibacterium acnes was significantly inhibited by ozenoxacin at concentrations from 1 to 30 μg ml −1. Likewise, the production of IL-6, IL-8, and tumor necrosis factor alpha by stimulated THP-1 cells, a human monocyte cell line, was inhibited by ozenoxacin at concentrations from 1 to 30 μg ml −1. The production of IL-1β by THP-1 was also inhibited by ozenoxacin at the concentration of 30 μg ml −1. Phosphorylation of the mitogen-activated protein kinases and degradation of IκB-α, an inhibitory factor of NF-κB in keratinocytes and THP-1 cells, was increased by stimulation with heat-killed C. acnes. Of these activated intracellular pathways, the p38 phosphorylation pathway was remarkably reduced by ozenoxacin in both keratinocytes and THP-1 cells. In addition, the application of 2% ozenoxacin suppressed the increase in the ear thickness of rats induced by an intracutaneous injection of heat-killed C. acnes. These findings suggest that ozenoxacin possesses an antiinflammatory activity, which may contribute to its therapeutic effects on inflammatory acne.
Background: Mucopolysaccharide polysulfate (MPS) is a heparinoid and MPS-containing formulations are widely used as moisturizers for dry skin and to treat peripheral vascular insufficiency. Although MPS has therapeutic effects in skin diseases with microvascular abnormalities, the effects of MPS on microvascular function remain incompletely understood. Objective: The aim of this study was to evaluate the functional activities of MPS on human pericytes (HPC) and human dermal microvascular endothelial cells (HDMEC) in vitro, and on microvascular permeability of the skin. Methods: The protein expression of angiopoietin (Ang)-1 in HPC, and platelet-derived growth factor-BB (PDGF-BB) and phosphorylated tyrosine-protein kinase receptor 2 (Tie2) in HDMEC were measured in the presence or absence of MPS. The vascular barrier was evaluated by the expressions of claudin-5 and vascular endothelial (VE)-cadherin, and transendothelial electrical resistance (TEER). Results: In HPC, MPS dose-dependently enhanced Ang-1 secretion, which activated Tie2 in HDMEC. In HDMEC, MPS significantly increased the production of PDGF-BB, which is important for the recruitment of HPC to the vascular endothelium, and significantly increased the phosphorylation of Tie2, which results in the activation of the Ang-1/Tie2 signaling . MPS significantly increased the expression of tight junction protein claudin-5 and TEER in the HDMEC. Moreover, the intradermal injection of MPS prevented vascular endothelial growth factor-induced increase in vascular permeability in mouse skin. Conclusion:We found that MPS promoted microvascular stabilization and barrier integrity in HDMEC via Ang-1/Tie2 activation. These results suggest that MPS might improve microvascular abnormalities in various diseases accompanied by disturbances in Ang-1/Tie2 signaling.
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