Molecular Blocking of CD23 Supports Its Role in the Pathogenesis of Arthritis

BACKGROUND: CD23 is a differentiation/activation antigen expressed by a variety of hematopoietic and epithelial cells. It can also be detected in soluble forms in biological fluids. Initially known as the low-affinity receptor for immunoglobulin E (Fc epsilonRII), CD23 displays various other physiologic ligands such as CD21, CD11b/c, CD47-vitronectin, and mannose-containing proteins. CD23 mediates numerous immune responses by enhancing IgE-specific antigen presentation, regulating IgE synthesis, influencing cell differentiation and growth of both B- and T-cells. CD23-crosslinking promotes the secretion of pro-inflammatory mediators from human monocytes/macrophages, eosinophils and epithelial cells. Increased CD23 expression is found in patients during allergic reactions and rheumatoid arthritis while its physiopathologic role in these diseases remains to be clarified. METHODOLOGY/PRINCIPAL FINDINGS: We previously generated heptapeptidic countrestructures of human CD23. Based on in vitro studies on healthy and arthritic patients' cells, we showed that CD23-specific peptide addition to human macrophages greatly diminished the transcription of genes encoding inflammatory cytokines. This was also confirmed by significant reduction of mediator levels in cell supernatants. We also show that CD23 peptide decreased IgE-mediated activation of both human and rat CD23(+) macrophages. In vivo studies in rat model of arthritis showed that CD23-blocking peptide ameliorates clinical scores and prevent bone destruction in a dose dependent manner. Ex-vivo analysis of rat macrophages further confirmed the inhibitory effect of peptides on their activation. Taken together our results support the role of CD23 activation and subsequent inflammatory response in arthritis. CONCLUSION: CD23-blocking peptide (p30A) prevents the activation of monocytes/macrophages without cell toxicity. Thus, targeting CD23 by antagonistic peptide decreases inflammatory markers and may have clinical value in the treatment of human arthritis and allergic reactions involving CD23

Comparison of CD23 staining patterns in Merkel cell carcinoma and non-cutaneous small cell carcinoma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72874/1/j.1600-0560.2008.00999.x.pd

Infection of hematopoietic stem cells by Leishmania infantum increases erythropoiesis and alters the phenotypic and functional profiles of progeny

Immunosuppression is a well-established risk factor for Visceral Leishmaniasis. Post-immunosuppression leishmaniasis is characterized by an increase of parasite burden, hematopoietic disorders and unusual clinical manifestations. Although there are many reports on bone marrow findings in VL, less is known about the relationship between parasite dynamics in this organ and the function of either hematopoietic stem cells and progenitor cells themselves. In the present study, we tackle these issues using a new approach of infecting human stem cells derived from bone marrow with L. infantum. Using this strategy, we show that human hematopoietic stem cells (hHSC) are able to phagocytize L. infantum promastigotes and release modulatory and pro-inflammatory cytokines, mainly TNF-α. Our results demonstrated that L. infantum infection in vitro enhances hematopoiesis, favoring the development of erythrocitic lineage through a mechanism yet unknown. Moreover, we found that L. infantum infection alters the phenotypic profile of the hematopoietic progeny; modifying the surface markers expression of differentiated cells. Thus, our study represents a rare opportunity to monitor the in vitro differentiation of human stem cells experimentally infected by L. infantum to better understand the consequences of the infection on phenotypic and functional profile of the cell progeny.Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) – APQ-000647-13, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) by fellowship awarded to LRVA, OAMF and ATC. RCG received fellowship from CNPq program. DM is supported by a PhD fellowship SFRH/BD/91543/2012, MR is supported by a PhD fellowship SFRH/BD/89871/2012. RS is supported by FCT Investigator 2014 (IF/00021/2014)info:eu-repo/semantics/publishedVersio

Pelargonidin-3-O-glucoside and its metabolites have modest anti-inflammatory effects in human whole blood cultures

This study hypothesized that the predominant strawberry anthocyanin, pelargonidin-3-O-glucoside (Pg-3-glc), and three of its plasma metabolites (4-hydroxybenzoic acid, protocatechuic acid and phloroglucinaldehyde [PGA]) would affect phagocytosis, oxidative burst and the production of selected pro- and anti-inflammatory cytokines in a whole blood culture model. For the assessment of phagocytosis and oxidative burst activity of monocytes and neutrophils, whole blood was pre-incubated in the presence or absence of the test compounds at concentrations up to 5 μM, followed by analysis of phagocytic and oxidative burst activity using commercially available test kits. For the cytokine analysis, diluted whole blood was stimulated with lipopolysaccharide in the presence or absence of the test compounds at concentrations up to 5 μM. Concentrations of selected cytokines (tumor necrosis factor-α [TNF-α], interleukin [IL]-1β, IL-6, IL-8 and IL-10) were determined using a cytometric bead array kit. There were no effects of any of the test compounds on phagocytosis of opsonized or non-opsonized E. coli or on oxidative burst activity. Pg-3-glc and PGA at 0.08 μM increased the concentration of IL-10 (P<0.01 and P<0.001, respectively), but there was no effect on TNF-α, IL-1β, IL-6 and IL-8 and there were no effects of the other compounds. In conclusion, this study demonstrated a lack of effect of these compounds on the opsonization, engulfment and subsequent destruction of bacteria. Pg-3-glc and PGA, at physiologically relevant concentrations, had anti-inflammatory properties; however, effects were modest, only observed at the lowest dose tested and limited to IL-10

Destructive arthritis in a patient with chikungunya virus infection with persistent specific IgM antibodies

<p>Abstract</p> <p>Background</p> <p>Chikungunya fever is an emerging arboviral disease characterized by an algo-eruptive syndrome, inflammatory polyarthralgias, or tenosynovitis that can last for months to years. Up to now, the pathophysiology of the chronic stage is poorly understood.</p> <p>Case presentation</p> <p>We report the first case of CHIKV infection with chronic associated rheumatism in a patient who developed progressive erosive arthritis with expression of inflammatory mediators and persistence of specific IgM antibodies over 24 months following infection.</p> <p>Conclusions</p> <p>Understanding the specific features of chikungunya virus as well as how the virus interacts with its host are essential for the prevention, treatment or cure of chikungunya disease.</p

Vaccination de la truite contre l'agent de la flavobactériose (mise au point de nanoparticules fonctionnalisées)

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Le récepteur nucléaire LxRa (régulation dans les cellules hépatiques HepG2 en vue de leur infection par le virus de l'hépatite C)

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Vaccination anti-papillomavirus humains (principes et état des lieux 2012)

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF