title: Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety.
abstract: Borrelia burgdorferi invasion of mammalian joints results in genesis of Lyme arthritis. Other than spirochete lipids, existence of protein antigens, which are abundant in joints and participate in B. burgdorferi-induced host inflammatory response, is unknown. Here, we report that major products of the B. burgdorferi basic membrane protein (bmp) A/B operon that are induced in murine and human joints, possess inflammatory properties. Compared to the wild type B. burgdorferi, an isogenic bmpA/B mutant induced significantly lower levels of pro-inflammatory cytokines TNF-alpha and IL-1beta in cultured human synovial cells, which could be restored using bmpA/B-complemented mutants, and more directly, upon addition of recombinant BmpA, but not BmpB or control spirochete proteins. Non-lipidated and lipidated versions of BmpA induced similar levels of cytokines, and remained unaffected by treatment with lipopolysaccharide inhibitor, polymyxin B. The bmpA/B mutant was also impaired in the induction of NF-kappaB and p38 MAP kinase signaling pathways in synovial cells, which were activated by non-lipidated BmpA. These results show that a protein moiety of BmpA can induce cytokine responses in synovial cells via activation of the NF-kappaB and p38 MAP kinase pathways and thus, could potentially contribute to the genesis of Lyme arthritis.
authors: Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
authors: Xiuli
authors: X
authors: Yang
authors: Hooman
authors: H
authors: Izadi
authors: Adam S
authors: AS
authors: Coleman
authors: Penghua
authors: P
authors: Wang
authors: Yongsheng
authors: Y
authors: Ma
authors: Erol
authors: E
authors: Fikrig
authors: Juan
authors: J
authors: Anguita
authors: Utpal
authors: U
authors: Pal
mesh_terms: D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000276:immunology / Q000472:pathogenicity*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008074:Lipoproteins / Q000276:immunology* / Q000378:metabolism; D008193:Lyme Disease / Q000276:immunology / Q000503:physiopathology; D016328:NF-kappa B / Q000378:metabolism; D013582:Synovial Fluid / Q000166:cytology* / Q000276:immunology / Q000382:microbiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D008074:Lipoproteins; D016328:NF-kappa B; C088728:P39 antigen, Borrelia burgdorferi; D048051:p38 Mitogen-Activated Protein Kinases