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

Biomedicine & Pharmacotherapy

Miaomiao Jian¹  Mingbiao Ma¹  Ruolan Bai²  Taigui Chen²  Lisha Luo³  Zhenhua Ji³  Fukai Bao⁴  Manzama-Esso Abi⁴  Lvyan Tao⁵  Aihua Liu⁵  Hua Zhao⁶  Zhe Ding⁶  Xinlin Han⁶  Xiting Dai⁶ 

[1] Corresponding authors at: Yunnan Province Key Laboratory for Tropical Infectious Diseases in Universities, Kunming Medical University, Kunming 650500, China.;The Institute for Tropical Medicine, Kunming Medical University, Kunming 650500, China;Yunnan Demonstration Base of International Science and Technology Cooperation for Tropical Diseases, Kunming 650500, China;Yunnan Province Key Laboratory for Tropical Infectious Diseases in Universities, Kunming Medical University, Kunming 650500, China;Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming 650500, China;Department of Microbiology and Immunology, Kunming Medical University, Kunming 650500, China;

关键词: Borrelia burgdorferi;    Lyme disease;    Lyme arthritis;    THP-1 cell;    Macrophage;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown