Study on the pro-inflammatory mechanism of the HuD antibody in promoting M1 polarization and paraneoplastic neurological syndrome occurrence

ABSTRACT

Paraneoplastic neurological syndrome (PNS) is a nonmetastatic complication of malignant tumors that may lead to immune-mediated neuronal dysfunction or death. The occurrence of PNS results from the binding of anti-neuronal antibodies to neuronal cell surface antigens or intracellular antigens, which hinders the function of target proteins and promotes cell death. The aim of this study is to research the effect and immune mechanism of the neuronal ELAV-like protein (HuD antibody) on PNS-related syndrome. Neuronal cells were co-cultured with monocyte macrophages with or without HuD antibody. Next, we detected the apoptosis of neuronal cells by flow cytometry. Meantime, macrophage M1/M2 polarization factors and the secretion of inflammatory factors in the co-culture system were also detected by quantitative polymerase chain reaction (qPCR), Western blots and ELISA technologies. The results showed that after adding the HuD antibody in the co-culture system, the apoptosis level of the neuroma cells were significantly increased, and the apoptosis level were not significant changed when co-culture with monocytes without HuD antibody. In addition, the level of factors of M1 macrophages TNF-α, IL-12, TGF-β and IFN-γ increased, while the level of factors of M2 macrophages IL-10, IL-4, and Arg-1 decreased. The outcomes demonstrated that absorption of the HuD antibody by cerebellar neuronal cells could promote the proliferation of M1 macrophages and stimulates macrophages to secrete inflammatory factors, further damage the neuronal cells, eventually resulting in the occurrence of PNS. This finding provided a theoretical basis for the subsequent treatment and prevention of PNS.

Graphical Abstract

KEYWORDS:

• Paraneoplastic neurological syndrome
• neuronal cells
• macrophages
• inflammatory factors

Highlights

1. The HuD antibody can be absorbed by the neuroma cells in the occurrence of PNS.

2. Neuroma cells promote the M1 macrophages when stimulated by HuD antibody.

3. M1 macrophages could damage the neuronal cells by secreting inflammatory factors.

Acknowledgements

We would like to acknowledge the hard and dedicated work of all the staff that implemented the intervention and evaluation components of the study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval and consent to participate

I confirm that I have read the Editorial Policy pages. This study was conducted with approval from the Ethics Committee of the First Affiliated Hospital of Bengbu Medical College (2020-182). This study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all participants.

Additional information

Funding

Key Special Project of Translational Medicine in Bengbu Medical College [BYTM2019030] Anhui Province University Natural Science Key Research Project [KJ2021A0728]