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Article

Increased Serum Levels of Brain-Derived Neurotrophic Factor Contribute to Inflammatory Responses in Patients with Rheumatoid Arthritis

1
Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chiayi 62247, Taiwan
2
School of Medicine, Tzu Chi University, Hualien City 97071, Taiwan
3
Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Minxiong, Chiayi 62130, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Chih-Hsin Tang
Int. J. Mol. Sci. 2021, 22(4), 1841; https://doi.org/10.3390/ijms22041841
Received: 28 January 2021 / Revised: 10 February 2021 / Accepted: 10 February 2021 / Published: 12 February 2021
(This article belongs to the Special Issue Research of Pathogenesis and Novel Therapeutics in Arthritis 3.0)
The aim of this study is to investigate the role of brain-derived neurotrophic factor (BDNF) in the inflammatory responses in patients with rheumatoid arthritis (RA). Serum levels of BDNF and the precursor form of BDNF (proBDNF) from 625 RA patients and 40 controls were analyzed using enzyme-linked immunosorbent assay. Effects of BDNF on the mitogen-activated protein kinase pathway were analyzed by Western blotting. Microarray analysis was conducted to search BDNF regulated gene expression in Jurkat cells, and the differentially expressed genes were validated using T cells from patients with RA and controls. Serum BDNF levels were significantly elevated in patients with RA compared with the controls. Low serum BDNF levels were found in RA patients with anxiety or receiving biologics treatment. BDNF (20 ng/mL) enhanced the phosphorylation of ERK, JNK, and c-Jun, but suppressed the phosphorylation of p38, whereas BDNF (200 ng/mL) enhanced the phosphorylation of ERK and p38. After validation, the expression of CAMK2A, MASP2, GNG13, and MUC5AC, regulated by BDNF and one of its receptors, NGFR, was increased in RA T cells. BDNF increased the IL-2, IL-17, and IFN-γ expression in Jurkat cells and IL-2 and IFN-γ secretion in activated peripheral blood mononuclear cells. View Full-Text
Keywords: BDNF; rheumatoid arthritis; JNK; T cells; anxiety; proinflammatory cytokines BDNF; rheumatoid arthritis; JNK; T cells; anxiety; proinflammatory cytokines
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MDPI and ACS Style

Lai, N.-S.; Yu, H.-C.; Huang Tseng, H.-Y.; Hsu, C.-W.; Huang, H.-B.; Lu, M.-C. Increased Serum Levels of Brain-Derived Neurotrophic Factor Contribute to Inflammatory Responses in Patients with Rheumatoid Arthritis. Int. J. Mol. Sci. 2021, 22, 1841. https://doi.org/10.3390/ijms22041841

AMA Style

Lai N-S, Yu H-C, Huang Tseng H-Y, Hsu C-W, Huang H-B, Lu M-C. Increased Serum Levels of Brain-Derived Neurotrophic Factor Contribute to Inflammatory Responses in Patients with Rheumatoid Arthritis. International Journal of Molecular Sciences. 2021; 22(4):1841. https://doi.org/10.3390/ijms22041841

Chicago/Turabian Style

Lai, Ning-Sheng, Hui-Chun Yu, Hsien-Yu Huang Tseng, Chia-Wen Hsu, Hsien-Bin Huang, and Ming-Chi Lu. 2021. "Increased Serum Levels of Brain-Derived Neurotrophic Factor Contribute to Inflammatory Responses in Patients with Rheumatoid Arthritis" International Journal of Molecular Sciences 22, no. 4: 1841. https://doi.org/10.3390/ijms22041841

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