A key protein from Borrelia burgdorferi could stimulate cytokines in human microglial cells and inhibitory effects of Cucurbitacin IIa

Xin Xu; Shiyuan Wen; Yu Zhang; Wenjing Cao; Peng Yue; Jing Kong; Meixiao Liu; Yuxin Fan; Jingjing Chen; Zhenhua Ji; Yan Dong; Guozhong Zhou; Bingxue Li; Aihua Liu; Fukai Bao

doi:10.1016/j.ibneur.2023.11.004

A key protein from Borrelia burgdorferi could stimulate cytokines in human microglial cells and inhibitory effects of Cucurbitacin IIa

IBRO Neurosci Rep. 2023 Nov 13:15:376-385. doi: 10.1016/j.ibneur.2023.11.004. eCollection 2023 Dec.

Authors

Xin Xu^{1

2

3}, Shiyuan Wen^{1

2

4}, Yu Zhang^{1

2

3}, Wenjing Cao^{1

5}, Peng Yue^{1

5}, Jing Kong^{1

2}, Meixiao Liu^{1

2}, Yuxin Fan^{1

2}, Jingjing Chen^{1

2}, Zhenhua Ji^{1

2}, Yan Dong^{1

2}, Guozhong Zhou^{1

2}, Bingxue Li^{1

2}, Aihua Liu^{1

2

3}, Fukai Bao^{1

2

3}

Affiliations

¹ The Institute for Tropical Medicine, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, China.
² Department of Microbiology and Immunology, Kunming Medical University, Kunming, China.
³ Yunnan Province Key Laboratory of Children's Major Diseases Research, The Affiliated Children Hospital, Kunming Medical University, Kunming, China.
⁴ Department of Intensive Care Unit, First People's Hospital of Yunnan Province, Kunming, China.
⁵ Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming, China.

Abstract

Lyme neuroborreliosis (LNB) is an infectious disease of the nervous system caused by Borrelia burgdorferi (Bb) infection. However, its pathogenesis is not fully understood. We used recombinant BmpA (rBmpA) to stimulate human microglia cell HMC3, then collected the culture supernatant and extracted total RNA from cells, and used the supernatant for cytokine chip, then ELISA and qPCR technology were used to validate the results from cytokine chip. After rBmpA stimulation of microglia, 24 inflammation-related cytokines showed elevated expression. Among them, six cytokines (IL-6, IL-8, CCL2, CCL5, CXCL1, and CXCL10) increased significantly in mRNA transcription, three cytokines (IL-6, IL-8, and CXCL10) concentrations in the cell supernatant increased significantly after the rBmpA stimulation, and CuIIa could inhibit expression of these cytokines. The BmpA can stimulate human microglia to produce large amounts of cytokines, leading to the occurrence of inflammation, which may be closely related to the development of LNB. CuIIa can inhibit BmpA-induced cytokine production in microglia, which may have potential therapeutic effects on LNB.

Keywords: Cucurbitacin IIa; Cytokine; Inflammation; Lyme neuroborreliosis; Microglia; RBmpA.