Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety.
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.
Yang
Xiuli
X
Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
Izadi
Hooman
H
Coleman
Adam S
AS
Wang
Penghua
P
Ma
Yongsheng
Y
Fikrig
Erol
E
Anguita
Juan
J
Pal
Utpal
U
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
D001426:Bacterial Proteins; D016207:Cytokines; D008074:Lipoproteins; D016328:NF-kappa B; C088728:P39 antigen, Borrelia burgdorferi; D048051:p38 Mitogen-Activated Protein Kinases