Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis

Qingtong Wang, Longsheng Wang, Li Wu, Mei Zhang, Shanshan Hu, Rui Wang, Yongsheng Han, Yujing Wu, Lingling Zhang, Xinming Wang, Wuyi Sun, Wei Wei

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

T cell infiltration to synovial tissue is an early pathogenic mechanism of rheumatoid arthritis (RA). In the present work, we reveal that G protein coupled receptor kinase 2 (GRK2) is abundantly expressed in T cells of collagen-induced arthritis (CIA). A GRK2 inhibitor, paroxetine protects the joints from inflammation and destruction, primarily through inhibition of both CD4 + helper T (Th) cell and CD8 + cytotoxic T (Tc) cell migration to synovial tissue. Meanwhile, paroxetine restores the balance of Th/Tc, effector Th (Theff)/ naïve Th (Thnaive) and effector Tc (Tceff)/ naïve Tc (Tcnaive) to equilibrium by elevating the frequency of Thnaive, Tcnaive and regulatory Th cells; reducing the increased Theff, activated Th and Tceff, having a similar effect as methotrexate (MTX). In addition, both serum and synovial IL-1β, TNF-α and CX3CL1 expression was effectively inhibited in treated rats. In vitro assay confirmed that paroxetine inhibits CX3CL1-induced T cell migration through blocking the activity of GRK2. Among three MAPK families, paroxetine was found to be able to decrease the phosphorylation of ERK. This study elucidates that paroxetine attenuates the symptoms of CIA rats due to its inhibitory effect on T cell activation and infiltration to synovial tissue via suppression of ERK pathway.

Original languageEnglish (US)
Article number45364
JournalScientific Reports
Volume7
DOIs
StatePublished - Mar 28 2017
Externally publishedYes

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Paroxetine
Experimental Arthritis
Lymphocyte Activation
G-Protein-Coupled Receptor Kinase 2
Joints
T-Lymphocytes
Cell Movement
MAP Kinase Signaling System
Helper-Inducer T-Lymphocytes
Interleukin-1
Methotrexate
Rheumatoid Arthritis
Phosphorylation
Inflammation
Serum

ASJC Scopus subject areas

  • General

Cite this

Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis. / Wang, Qingtong; Wang, Longsheng; Wu, Li; Zhang, Mei; Hu, Shanshan; Wang, Rui; Han, Yongsheng; Wu, Yujing; Zhang, Lingling; Wang, Xinming; Sun, Wuyi; Wei, Wei.

In: Scientific Reports, Vol. 7, 45364, 28.03.2017.

Research output: Contribution to journalArticle

Wang, Q, Wang, L, Wu, L, Zhang, M, Hu, S, Wang, R, Han, Y, Wu, Y, Zhang, L, Wang, X, Sun, W & Wei, W 2017, 'Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis', Scientific Reports, vol. 7, 45364. https://doi.org/10.1038/srep45364
Wang, Qingtong ; Wang, Longsheng ; Wu, Li ; Zhang, Mei ; Hu, Shanshan ; Wang, Rui ; Han, Yongsheng ; Wu, Yujing ; Zhang, Lingling ; Wang, Xinming ; Sun, Wuyi ; Wei, Wei. / Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis. In: Scientific Reports. 2017 ; Vol. 7.
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abstract = "T cell infiltration to synovial tissue is an early pathogenic mechanism of rheumatoid arthritis (RA). In the present work, we reveal that G protein coupled receptor kinase 2 (GRK2) is abundantly expressed in T cells of collagen-induced arthritis (CIA). A GRK2 inhibitor, paroxetine protects the joints from inflammation and destruction, primarily through inhibition of both CD4 + helper T (Th) cell and CD8 + cytotoxic T (Tc) cell migration to synovial tissue. Meanwhile, paroxetine restores the balance of Th/Tc, effector Th (Theff)/ na{\"i}ve Th (Thnaive) and effector Tc (Tceff)/ na{\"i}ve Tc (Tcnaive) to equilibrium by elevating the frequency of Thnaive, Tcnaive and regulatory Th cells; reducing the increased Theff, activated Th and Tceff, having a similar effect as methotrexate (MTX). In addition, both serum and synovial IL-1β, TNF-α and CX3CL1 expression was effectively inhibited in treated rats. In vitro assay confirmed that paroxetine inhibits CX3CL1-induced T cell migration through blocking the activity of GRK2. Among three MAPK families, paroxetine was found to be able to decrease the phosphorylation of ERK. This study elucidates that paroxetine attenuates the symptoms of CIA rats due to its inhibitory effect on T cell activation and infiltration to synovial tissue via suppression of ERK pathway.",
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