TY  - JOUR
AU  - Wang, Mingjun
AU  - Harhaji-Trajković, Ljubica
AU  - Lamberth, K
AU  - Harndahl, M
AU  - Buus, S
AU  - Heegaard, NHH
AU  - Claesson, MH
AU  - Nissen, Mogens H
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1463
AB  - Beta2-microglobulin (beta 2m) is the light chain of major histocompatibility complex class I (MHC-I) molecules, and is a prerequisite for the binding of peptides to the heavy chain and their presentation to CD8(+) T cells. beta 2m can be modified in vivo and in vitro by proteolytic cleavage by complement C1 and subsequent carboxypeptidase B-like activity - processes that lead to the generation of desLys(58)beta 2m (d beta 2m). This work aims to study the effect of d beta 2m on peptide binding to MHC-I, the influence of d beta 2m on the binding of beta 2m to the MHC-I heavy chain and the biological activity of d beta 2m. Both beta 2m and d beta 2m are able to support the generation of MHC-I/peptide complexes at 18 degrees C, but complexes formed in the presence of d beta 2m destabilize at 37 degrees C. Moreover, a 250 times higher concentration of d beta 2m than of beta 2m is needed to displace MHC-I associated beta 2m from the cell surface. In addition, only beta 2m is able to restore MHC-I/peptide complex formation on acid-treated cells whereas d beta 2m appears to bind preferentially to denatured MHC-I heavy chains. In cell cultures, exogenously added d beta 2m, but not beta 2m, induces apoptotic cell death in monocytic leukaemic cell lines but spares other kinds of leukaemic cells. Additionally, the presence of d beta 2m, and to a lesser extent beta 2m, enhances IFN-gamma-induced NO production by monocytic leukaemic cells. In conclusion, these data show that d beta 2m is not able to support the formation of a stable tri-molecular MHC-I complex at physiological temperature and that d beta 2m exerts other biological functions compared to beta 2m when bound to cells.
T2  - Scandinavian Journal of Immunology
T1  - Modified Human Beta 2-Microglobulin (desLys(58)) Displays Decreased Affinity for the Heavy Chain of MHC Class I and Induces Nitric Oxide Production and Apoptosis
IS  - 3
VL  - 69
EP  - 212
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1463
ER  - 

@article{
author = "Wang, Mingjun and Harhaji-Trajković, Ljubica and Lamberth, K and Harndahl, M and Buus, S and Heegaard, NHH and Claesson, MH and Nissen, Mogens H",
year = "2009",
abstract = "Beta2-microglobulin (beta 2m) is the light chain of major histocompatibility complex class I (MHC-I) molecules, and is a prerequisite for the binding of peptides to the heavy chain and their presentation to CD8(+) T cells. beta 2m can be modified in vivo and in vitro by proteolytic cleavage by complement C1 and subsequent carboxypeptidase B-like activity - processes that lead to the generation of desLys(58)beta 2m (d beta 2m). This work aims to study the effect of d beta 2m on peptide binding to MHC-I, the influence of d beta 2m on the binding of beta 2m to the MHC-I heavy chain and the biological activity of d beta 2m. Both beta 2m and d beta 2m are able to support the generation of MHC-I/peptide complexes at 18 degrees C, but complexes formed in the presence of d beta 2m destabilize at 37 degrees C. Moreover, a 250 times higher concentration of d beta 2m than of beta 2m is needed to displace MHC-I associated beta 2m from the cell surface. In addition, only beta 2m is able to restore MHC-I/peptide complex formation on acid-treated cells whereas d beta 2m appears to bind preferentially to denatured MHC-I heavy chains. In cell cultures, exogenously added d beta 2m, but not beta 2m, induces apoptotic cell death in monocytic leukaemic cell lines but spares other kinds of leukaemic cells. Additionally, the presence of d beta 2m, and to a lesser extent beta 2m, enhances IFN-gamma-induced NO production by monocytic leukaemic cells. In conclusion, these data show that d beta 2m is not able to support the formation of a stable tri-molecular MHC-I complex at physiological temperature and that d beta 2m exerts other biological functions compared to beta 2m when bound to cells.",
journal = "Scandinavian Journal of Immunology",
title = "Modified Human Beta 2-Microglobulin (desLys(58)) Displays Decreased Affinity for the Heavy Chain of MHC Class I and Induces Nitric Oxide Production and Apoptosis",
number = "3",
volume = "69",
pages = "212",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1463"
}

Wang, M., Harhaji-Trajković, L., Lamberth, K., Harndahl, M., Buus, S., Heegaard, N., Claesson, M.,& Nissen, M. H.. (2009). Modified Human Beta 2-Microglobulin (desLys(58)) Displays Decreased Affinity for the Heavy Chain of MHC Class I and Induces Nitric Oxide Production and Apoptosis. in Scandinavian Journal of Immunology, 69(3).
https://hdl.handle.net/21.15107/rcub_ibiss_1463

Wang M, Harhaji-Trajković L, Lamberth K, Harndahl M, Buus S, Heegaard N, Claesson M, Nissen MH. Modified Human Beta 2-Microglobulin (desLys(58)) Displays Decreased Affinity for the Heavy Chain of MHC Class I and Induces Nitric Oxide Production and Apoptosis. in Scandinavian Journal of Immunology. 2009;69(3):null-212.
https://hdl.handle.net/21.15107/rcub_ibiss_1463 .

Wang, Mingjun, Harhaji-Trajković, Ljubica, Lamberth, K, Harndahl, M, Buus, S, Heegaard, NHH, Claesson, MH, Nissen, Mogens H, "Modified Human Beta 2-Microglobulin (desLys(58)) Displays Decreased Affinity for the Heavy Chain of MHC Class I and Induces Nitric Oxide Production and Apoptosis" in Scandinavian Journal of Immunology, 69, no. 3 (2009),
https://hdl.handle.net/21.15107/rcub_ibiss_1463 .

TY  - JOUR
AU  - Claesson, MH
AU  - Nicoletti, Ferdinando
AU  - Stošić-Grujičić, Stanislava
AU  - Doria, A
AU  - Zampieri, S
PY  - 2008
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1550
AB  - Type 1 diabetes mellitus (T1D) and inflammmtory bowel diseases (IBD) are multifactorial disorders of autoimmune origin. Several microbial agents have been reported to be associated with the development of type 1 diabetes and inflammatory bowel diseases in animal models by different mechanisms. These models which resemble the phenotype of the human disease they mimic, can be very useful to identify important pathogenetic mechanisms, as well as therapeutical targets to treat the disease. This review is focused on the immune inflammatory pathways which are considered to be associated with the pathogenesis T1D and IBD in transgenic mice.
T2  - Clinical and Experimental Rheumatology
T1  - Interactions between infections and immune-inflammatory cells in type 1 diabetes mellitus and inflammatory bowel diseases: evidences from animal models
IS  - 1
VL  - 26
EP  - S11
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1550
ER  - 

@article{
author = "Claesson, MH and Nicoletti, Ferdinando and Stošić-Grujičić, Stanislava and Doria, A and Zampieri, S",
year = "2008",
abstract = "Type 1 diabetes mellitus (T1D) and inflammmtory bowel diseases (IBD) are multifactorial disorders of autoimmune origin. Several microbial agents have been reported to be associated with the development of type 1 diabetes and inflammatory bowel diseases in animal models by different mechanisms. These models which resemble the phenotype of the human disease they mimic, can be very useful to identify important pathogenetic mechanisms, as well as therapeutical targets to treat the disease. This review is focused on the immune inflammatory pathways which are considered to be associated with the pathogenesis T1D and IBD in transgenic mice.",
journal = "Clinical and Experimental Rheumatology",
title = "Interactions between infections and immune-inflammatory cells in type 1 diabetes mellitus and inflammatory bowel diseases: evidences from animal models",
number = "1",
volume = "26",
pages = "S11",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1550"
}

Claesson, M., Nicoletti, F., Stošić-Grujičić, S., Doria, A.,& Zampieri, S.. (2008). Interactions between infections and immune-inflammatory cells in type 1 diabetes mellitus and inflammatory bowel diseases: evidences from animal models. in Clinical and Experimental Rheumatology, 26(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1550

Claesson M, Nicoletti F, Stošić-Grujičić S, Doria A, Zampieri S. Interactions between infections and immune-inflammatory cells in type 1 diabetes mellitus and inflammatory bowel diseases: evidences from animal models. in Clinical and Experimental Rheumatology. 2008;26(1):null-S11.
https://hdl.handle.net/21.15107/rcub_ibiss_1550 .

Claesson, MH, Nicoletti, Ferdinando, Stošić-Grujičić, Stanislava, Doria, A, Zampieri, S, "Interactions between infections and immune-inflammatory cells in type 1 diabetes mellitus and inflammatory bowel diseases: evidences from animal models" in Clinical and Experimental Rheumatology, 26, no. 1 (2008),
https://hdl.handle.net/21.15107/rcub_ibiss_1550 .

TY  - JOUR
AU  - Stojanović, Ivana D.
AU  - Cuzzocrea, S
AU  - Mangano, Katia
AU  - Mazzon, E
AU  - Miljković, Đorđe
AU  - Wang, MJ
AU  - Donia, Marco
AU  - Al-Abed, Yousef
AU  - Kim, Joseph
AU  - Nicoletti, Ferdinando
AU  - Stošić-Grujičić, Stanislava
AU  - Claesson, MH
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1598
AB  - We have presently studied the in vitro, ex vivo and in vivo immunopharmacological effects of VGX-1027 [(S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid]. This compound reduced the secretion of IL-1 beta, TNF-alpha and IL-10 from purified murine macrophages stimulated "in vitro" with lipopolysaccharide (LPS), and it also modified the signaling pathways induced in these cells by LPS entailing reduced activation of NF-kappa B and p38 MAP kinase pathways along with up-regulation of ERK pathways. VGX-1027 appeared to spare T cell function as it was unable to modify the proliferation and/or secretion of IL-2, IFN-gamma and IL-4 induced in purified murine CD4(+) T cells from stimulation with either CD3(+)CD28 or ConA. These effects on macrophages may account for the capacity of VGX-1027 to markedly ameliorate the course of both acute and chronic immunoinflammatory diseases in mice such as carrageenan-induced pleurisy, LPS-induced lethality and type II collagen-induced arthritis. Acute and subacute toxicological studies show that the drug is not toxic at the doses that exert biological effects in these preclinical models. These data warrant additional studies for the potential use of VGX-1027 in the clinical setting. (C) 2007 Elsevier Inc. All rights reserved.
T2  - Clinical Immunology
T1  - In vitro, ex vivo and in vivo immunopharmacological activities of the isoxazoline compound VGX-1027: Modulation of cytokine synthesis and prevention of both organ-specific and systemic autoimmune diseases in murine models
IS  - 3
VL  - 123
EP  - 323
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1598
ER  - 

@article{
author = "Stojanović, Ivana D. and Cuzzocrea, S and Mangano, Katia and Mazzon, E and Miljković, Đorđe and Wang, MJ and Donia, Marco and Al-Abed, Yousef and Kim, Joseph and Nicoletti, Ferdinando and Stošić-Grujičić, Stanislava and Claesson, MH",
year = "2007",
abstract = "We have presently studied the in vitro, ex vivo and in vivo immunopharmacological effects of VGX-1027 [(S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid]. This compound reduced the secretion of IL-1 beta, TNF-alpha and IL-10 from purified murine macrophages stimulated "in vitro" with lipopolysaccharide (LPS), and it also modified the signaling pathways induced in these cells by LPS entailing reduced activation of NF-kappa B and p38 MAP kinase pathways along with up-regulation of ERK pathways. VGX-1027 appeared to spare T cell function as it was unable to modify the proliferation and/or secretion of IL-2, IFN-gamma and IL-4 induced in purified murine CD4(+) T cells from stimulation with either CD3(+)CD28 or ConA. These effects on macrophages may account for the capacity of VGX-1027 to markedly ameliorate the course of both acute and chronic immunoinflammatory diseases in mice such as carrageenan-induced pleurisy, LPS-induced lethality and type II collagen-induced arthritis. Acute and subacute toxicological studies show that the drug is not toxic at the doses that exert biological effects in these preclinical models. These data warrant additional studies for the potential use of VGX-1027 in the clinical setting. (C) 2007 Elsevier Inc. All rights reserved.",
journal = "Clinical Immunology",
title = "In vitro, ex vivo and in vivo immunopharmacological activities of the isoxazoline compound VGX-1027: Modulation of cytokine synthesis and prevention of both organ-specific and systemic autoimmune diseases in murine models",
number = "3",
volume = "123",
pages = "323",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1598"
}

Stojanović, I. D., Cuzzocrea, S., Mangano, K., Mazzon, E., Miljković, Đ., Wang, M., Donia, M., Al-Abed, Y., Kim, J., Nicoletti, F., Stošić-Grujičić, S.,& Claesson, M.. (2007). In vitro, ex vivo and in vivo immunopharmacological activities of the isoxazoline compound VGX-1027: Modulation of cytokine synthesis and prevention of both organ-specific and systemic autoimmune diseases in murine models. in Clinical Immunology, 123(3).
https://hdl.handle.net/21.15107/rcub_ibiss_1598

Stojanović ID, Cuzzocrea S, Mangano K, Mazzon E, Miljković Đ, Wang M, Donia M, Al-Abed Y, Kim J, Nicoletti F, Stošić-Grujičić S, Claesson M. In vitro, ex vivo and in vivo immunopharmacological activities of the isoxazoline compound VGX-1027: Modulation of cytokine synthesis and prevention of both organ-specific and systemic autoimmune diseases in murine models. in Clinical Immunology. 2007;123(3):null-323.
https://hdl.handle.net/21.15107/rcub_ibiss_1598 .

Stojanović, Ivana D., Cuzzocrea, S, Mangano, Katia, Mazzon, E, Miljković, Đorđe, Wang, MJ, Donia, Marco, Al-Abed, Yousef, Kim, Joseph, Nicoletti, Ferdinando, Stošić-Grujičić, Stanislava, Claesson, MH, "In vitro, ex vivo and in vivo immunopharmacological activities of the isoxazoline compound VGX-1027: Modulation of cytokine synthesis and prevention of both organ-specific and systemic autoimmune diseases in murine models" in Clinical Immunology, 123, no. 3 (2007),
https://hdl.handle.net/21.15107/rcub_ibiss_1598 .