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Jalel A.,Research Unit on the Antioxidant Compounds | Ridha A.,Research Unit on the Antioxidant Compounds | Laurent D.,Hospital Foschi | Philippe M.,Laboratory of Immunogenetics | Hamdaoui M.,Research Unit on the Antioxidant Compounds
Indian Journal of Dermatology | Year: 2010

Background: The human leukocyte antigen (HLA) system in the skin coordinates the pigmentation and immune response and could be implicated in the pathogenesis of vitiligo. Human leukocyte antigen HLA-G is a nonclassic, major histocompatibility complex class I molecule expressed in the extravillous cytotrophoblast at the feto-maternal interface. It is known to protect the fetus from maternal cellular immunity. Analogically, it could be implicated in the pathogenesis of autoimmune diseases such as vitiligo. Aims: To compare the expression of HLA-G between vitiligo patients and healthy controls. Materials and Methods: In the present study, 22 vitiligo patients and 24 healthy controls were investigated to look for a possible correlation between HLA-G expression and this pathology. Expression of HLA-G in cutaneous biopsy specimens was investigated by immunohistochemical analysis. Results: HLA-G was detected in the biopsy specimens of 3 (13%) out of 22 patients. This number was significantly higher in healthy controls 18 (75%) out of 24 as compared to vitiligo patients ( P < 0.001). Conclusion: There is significant negative correlation between HLA-G expression and vitiligo. In our mind, upregulation of HLA-G expression in lesional skin could be local (superficial expression) or systemic (soluble HLA-G isoforms) compensation to restore normal pigmentation in lesions. Source


Oliveira A.C.,Masters Program in Health science | Mattos L.C.,Laboratory of Immunogenetics | Cavasini C.E.,Center for Investigation of Microorganisms
Journal of Venomous Animals and Toxins Including Tropical Diseases | Year: 2011

Dufy gene (FY) codifes the transmembrane glycoprotein Dufy (gp-Fy) of 35 to 43 kDa which is moderately immunogenic. This glycoprotein is polymorphic, and constitutes the antigens of the Dufy histo-blood system which were designated receptors for chemokines and denominated DARC (Dufy antigen/receptor for chemokine). This receptor has an important role in the regulation of chemokine levels in the circulation, as it binds and adsorbs them on the surface of red cells as a reservoir. It plays a "sink" role, which can contribute to homeostasis by removing infammatory chemokines from circulation as well as maintaining them in plasmatic levels. Chronic Chagas' cardiopathy (CCC) is the most frequent form of the disease. It is an infammatory disease, in which infltrated infammatory cells play an important role in the development and progress of the infection. High chemokine levels in the plasma have been associated with the disease severity in patients with heart failure. In this context, the profle of DARC expression could play an important function as a receptor for chemokines in Chagas' disease, in patients with CCC, as it can modulate damage from this infammatory disease. Source


Joyce M.G.,University of Leicester | Joyce M.G.,Laboratory of Immunogenetics | Ekanem I.S.,University of Manchester | Roitel O.,University of Leicester | And 7 more authors.
FEBS Journal | Year: 2012

We report the crystal structure of the FAD/NADPH-binding domain (FAD domain) of the biotechnologically important Bacillus megaterium flavocytochrome P450 BM3, the last domain of the enzyme to be structurally resolved. The structure was solved in both the absence and presence of the ligand NADP +, identifying important protein interactions with the NADPH 2'-phosphate that helps to dictate specificity for NADPH over NADH, and involving residues Tyr974, Arg966, Lys972 and Ser965. The Trp1046 side chain shields the FAD isoalloxazine ring from NADPH, and motion of this residue is required to enable NADPH-dependent FAD reduction. Multiple binding interactions stabilize the FAD cofactor, including aromatic stacking with the adenine group from the side chains of Tyr860 and Trp854, and several interactions with FAD pyrophosphate oxygens, including bonding to tyrosines 828, 829 and 860. Mutagenesis of C773 and C999 to alanine was required for successful crystallization, with C773A predicted to disfavour intramolecular and intermolecular disulfide bonding. Multiangle laser light scattering analysis showed wild-type FAD domain to be near-exclusively dimeric, with dimer disruption achieved on treatment with the reducing agent dithiothreitol. By contrast, light scattering showed that the C773A/C999A FAD domain was monomeric. The C773A/C999A FAD domain structure confirms that Ala773 is surface exposed and in close proximity to Cys810, with this region of the enzyme's connecting domain (that links the FAD domain to the FMN-binding domain in P450 BM3) located at a crystal contact interface between FAD domains. The FAD domain crystal structure enables molecular modelling of its interactions with its cognate FMN (flavodoxin-like) domain within the BM3 reductase module. © 2012 FEBS. Source


Zinocker S.,University of Oslo | Zinocker S.,Laboratory of Immunogenetics | Vaage J.T.,University of Oslo
Frontiers in Immunology | Year: 2012

Mesenchymal stromal cells (MSC) have important immunomodulatory properties, they inhibit T lymphocyte allo-activation and have been used to treat graft-versus-host disease. How MSC exert their immunosuppressive functions is not completely understood but species specific mechanisms have been implicated. In this study we have investigated the mechanisms for rat MSC mediated inhibition ofT lymphocyte proliferation and secretion of inflammatory cytokines in response to allogeneic and mitogenic stimuli in vitro. MSC inhibited the proliferation of T cells in allogeneic mixed lymphocyte reactions and in response to mitogen with similar efficacy. The anti-proliferative effect was mediated by the induced expression of nitric oxide (NO) synthase and production of NO by MSC. This pathway was required and sufficient to fully suppress lymphocyte proliferation and depended on proximity of MSC and target cells. Expression of inducible NO synthase by MSC was induced through synergistic stimulation with tumor necrosis factor α and interferon γ secreted by activated lymphocytes. Conversely, MSC had a pronounced inhibitory effect on the secretion of these cytokines by T cells which did not depend on NO synthase activity or cell contact, but was partially reversed by addition of the cyclooxygenase (COX) inhibitor indomethacin. In conclusion, rat MSC use different mechanisms to inhibit proliferative and inflammatory responses of activated T cells. While proliferation is suppressed by production of NO, cytokine secretion appears to be impaired at least in part by COX-dependent production of prostaglandin E2. © 2012. Source


Murakami Y.,Laboratory of Immunogenetics
Clinical calcium | Year: 2010

Cytokines have an essential role for cell-cell communication. They can regulate cell proliferation, differentiation, survival, and function. Interaction of cell surface receptor with cytokines is necessary for control of physiological responses. Activation of cytokine receptors transduces specific signal in the receptor-expressing cells, resulting that cytokines can regulate specific cell population. Thus, cytokines contribute directly or indirectly to morphogenesis, host defense and immune response, play critical roles for homeostasis and development. Source

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