Borrelia burgdorferi basic membrane protein A initiates proinflammatory chemokine storm in THP 1-derived macrophages via the receptors TLR1 and TLR2.

Authors:
Hua Zhao
Hua Zhao
The First Affiliated Hospital of Soochow University
China
Xinlin Han
Xinlin Han
1 Yunnan Province Key Laboratory for Tropical Infectious Diseases in Universities
China
Aihua Liu
Aihua Liu
Qingdao Institute of Bioenergy & Bioprocess Technology
China
Ruolan Bai
Ruolan Bai
Chengdu Medical College
Chengdu Shi | China
Zhenhua Ji
Zhenhua Ji
Kunming Medical University
Kunming Shi | China
Miaomiao Jian
Miaomiao Jian
Kunming Medical University
Kunming Shi | China

Biomed Pharmacother 2019 Apr 16;115:108874. Epub 2019 Apr 16.

Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming 650500, China.

Lyme disease, reffered to as Lyme borreliosis, is a tick-borne zoonotic disease caused by Borrelia burgdorferi spirochetes. Lyme arthritis, the most common, serious and harmful manifestation during the late stages of Lyme disease, is closely associated with the Borrelia burgdorferi basic membrane protein A (BmpA). Chemokines are also reported to have an important role in Lyme arthritis. Toll-like receptors (TLRs) recognize and bind to pathogen-associated molecules which are structurally conserved among microbes, to activate transcriptional events, including cytokine production, inflammation, and tissue damage. We speculated that BmpA could induce a storm of proinflammatory chemokines via TLRs and downstream moleculars, and that TLR1, TLR2, TLR5, TLR6 and the adaptor protein, MyD88, may be involved in this process. We explored this hypothesis using the human monocytic leukemia cell line, THP-1, and recombinant BmpA (rBmpA). Cell surface TLR1 and TLR2 were neutralized using specific antibodies before stimulation with rBmpA and analysis of chemokine secretion using a chemokine chip. Further, the expressions level of the four TLRs and MyD88 were analyzed following stimulation with rBmpA. Stimulation with rBmpA resulted in elevated levels of seven cytokines. Further, TLR1 and TLR2 antibody treated cells exhibited an overall reduction in rBmpA-induced chemokine expression. TLR1, TLR2, and MyD88 expression levels (both mRNA and protein) increased after stimulation with rBmpA. Our data confirm that TLR1, TLR2, and MyD88 are involved in BmpA-induced proinflammatory chemokines, which may be closely involved in Lyme arthritis pathogenesis.

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http://dx.doi.org/10.1016/j.biopha.2019.108874DOI Listing
April 2019
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