title: Angiocidin promotes pro-inflammatory cytokine production and antigen presentation in multiple sclerosis.
abstract: Angiocidin was originally identified as a potent inhibitor of angiogenesis and tumor growth in vivo. In addition to its involvement in the regulation of carcinogenesis, recent studies indicate that angiocidin may also play a significant role in immune system modulation. This report describes the expression and potential function of angiocidin in multiple sclerosis (MS), a severe demyelinating, inflammatory and autoimmune disease of the central nervous system (CNS). We demonstrated that angiocidin and interleukin-7 (IL-7) are over-expressed in brain lesions of MS patients. Angiocidin-treated monocytes, peripheral blood T cells and primary astrocytes secreted various cytokines and chemokines including, IL-6, IL-7, GM-CSF, and MCP-1. Addition of recombinant angiocidin to cell cultures was able to promote differentiation of monocytes into a macrophage-like cell, induce MHC class I and class II gene expression and activate CD4(+) and CD8(+) T lymphocytes. Consistent with these findings, angiocidin induced mononuclear phagocyte migration and adhesion as well as increased the IL-2 response by antigen-specific T cells to myelin basic protein peptide presented to them by autologous mononuclear phagocytes. Furthermore, we examined STAT3 expression in angiocidin stimulated mononuclear phagocytes, T cells, and primary astrocytes. We found that angiocidin markedly stimulates STAT3 expression in these cell populations. Angiocidin, therefore appears to play a previously unappreciated and potentially important role in the regulation of immune response during the clinical course of MS.
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, PA 19122, United States. skremlev@temple.edu
authors.forename: Sergey G
authors.initials: SG
authors.lastname: Kremlev
authors.forename: Anita L
authors.initials: AL
authors.lastname: Gaurnier-Hausser
authors.forename: Luis
authors.initials: L
authors.lastname: Del Valle
authors.forename: Georgina
authors.initials: G
authors.lastname: Perez-Liz
authors.forename: Svetoslav
authors.initials: S
authors.lastname: Dimitrov
authors.forename: George
authors.initials: G
authors.lastname: Tuszynski
mesh_terms: D000368:Aged; D017951:Antigen Presentation / Q000187:drug effects / Q000502:physiology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006680:HLA Antigens / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D015851:Interleukin-7 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D006680:HLA Antigens; C508605:IL7 protein, human; D015851:Interleukin-7; C498506:PSMD4 protein, human; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D046988:Proteasome Endopeptidase Complex