27 February 2018 : Animal Research
Norepinephrine Inhibits Th17 Cells via β2-Adrenergic Receptor (β2-AR) Signaling in a Mouse Model of Rheumatoid Arthritis
Yan Liu12BCD, Xiao-Xiao Rui2BC, Hui Shi2BC, Yi-Hua Qiu2ADG*, Yu-Ping Peng2ADEFGDOI: 10.12659/MSM.906184
Med Sci Monit 2018; 24: ANS1196-1204
Abstract
BACKGROUND: Norepinephrine (NE), a neurotransmitter released from the sympathetic nerves, has been shown to be involved in rheumatoid arthritis (RA). However, its role in the sympathetic nervous system in RA is divergent. Herein, we demonstrate that the sympathetic neurotransmitter NE exerts an anti-inflammatory effect in collagen-induced arthritis (CIA), a mouse model of RA, by inhibiting Th17 cell differentiation and function via β2-adrenergic receptor (β2-AR) signaling.
MATERIAL AND METHODS: CIA was prepared by intradermal injection of collagen type II in the tail base of DBA1/J mice. On the 41st day post-immunization, the mice were used as CIA models. CD4+ T cells from the spleen were purified using magnetic cell sorting and activated with anti-CD3 anti-CD28 antibodies. Th17 cells were polarized from the CD4+ T cells using various antibodies and cytokines.
RESULTS: Co-expression of CD4 and β2-AR was observed in spleens of both intact and CIA mice. The β2-AR expression in the ankle and spleen was downregulated in CIA mice. CIA induced increases in production of interleukin (IL)-17 and IL-22, CD25–IL-17+ cell percentage, and ROR-γt expression in CD4+ T cells. Importantly, NE reduced the CIA-induced CD4+ T cell shift towards Th17 phenotype, and the β2-AR antagonist ICI118551 blocked the NE effect. Moreover, the β2-AR agonist terbutaline (Terb) inhibited CIA-induced CD4+ T cell proliferation and shift towards Th17 phenotype, and the protein kinase A (PKA) inhibitor H-89 abolished the agonist effect. Terb also reduced CIA-induced Th17 enhancement, and H-89 impaired the Terb effect.
CONCLUSIONS: NE inhibits Th17 cell differentiation and function in CIA condition by activation of β2-AR/PKA signaling.
Keywords: Arthritis, Experimental, CD4-Positive T-Lymphocytes, Norepinephrine, Receptors, Adrenergic, Th17 Cells
Editorial
01 March 2024 : Editorial
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-ThalassemiaDOI: 10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
In Press
18 Mar 2024 : Clinical Research
Sexual Dysfunction in Women After Tibial Fracture: A Retrospective Comparative StudyMed Sci Monit In Press; DOI: 10.12659/MSM.944136
21 Feb 2024 : Clinical Research
Potential Value of HSP90α in Prognosis of Triple-Negative Breast CancerMed Sci Monit In Press; DOI: 10.12659/MSM.943049
22 Feb 2024 : Review article
Differentiation of Native Vertebral Osteomyelitis: A Comprehensive Review of Imaging Techniques and Future ...Med Sci Monit In Press; DOI: 10.12659/MSM.943168
23 Feb 2024 : Clinical Research
A Study of 60 Patients with Low Back Pain to Compare Outcomes Following Magnetotherapy, Ultrasound, Laser, ...Med Sci Monit In Press; DOI: 10.12659/MSM.943732
Most Viewed Current Articles
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952