title: Alpha 1 Antitrypsin Inhibits Dendritic Cell Activation and Attenuates Nephritis in a Mouse Model of Lupus.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution and considerable mortality and morbidity. Although the pathogenesis of this disease remains elusive, over-reactive dendritic cells (DCs) play a critical role in the disease development. It has been shown that human alpha-1 antitrypsin (hAAT) has protective effects in type 1 diabetes and rheumatoid arthritis mouse models. In the present study, we tested the effect of AAT on DC differentiation and functions, as well as its protective effect in a lupus-prone mouse model. We showed that hAAT treatment significantly inhibited LPS (TLR4 agonist) and CpG (TLR9 agonist) -induced bone-marrow (BM)-derived conventional and plasmacytoid DC (cDC and pDC) activation and reduced the production of inflammatory cytokines including IFN-I, TNF-α and IL-1β. In MRL/lpr mice, hAAT treatment significantly reduced BM-derived DC differentiation, serum autoantibody levels, and importantly attenuated renal pathology. Our results for the first time demonstrate that hAAT inhibits DC activation and function, and it also attenuates autoimmunity and renal damage in the MRL/lpr lupus model. These results imply that hAAT has a therapeutic potential for the treatment of SLE in humans.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.|Department of Pharmaceutics, Zagazig University, Zagazig, Sharkia, Egypt.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Elshikha
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Mong-Jen
authors.initials: MJ
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Akbar
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Leilani
authors.initials: L
authors.lastname: Zeumer
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ritter
authors.affiliation: Department of Pharmaceutics, Zagazig University, Zagazig, Sharkia, Egypt.
authors.forename: Hanaa
authors.initials: H
authors.lastname: Elghamry
authors.affiliation: Department of Pharmaceutics, Zagazig University, Zagazig, Sharkia, Egypt.
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Mahdi
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Laurence
authors.initials: L
authors.lastname: Morel
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Sihong
authors.initials: S
authors.lastname: Song
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D000515:alpha 1-Antitrypsin