Regulation of PGE2 signaling pathways and TNF-alpha signaling pathways on the function of bone marrow-derived dendritic cells and the effects of CP-25

Liu, Ying; Sheng, Kangliang; Chen, Jingyu; Wu, Yujing; Zhang, Feng; Cao, Yan; Wu, Huaxun; Fu, Jingjing; Zhang, Lingling; Wei, Wei

doi:10.1016/j.ejphar.2015.09.036

Cited by 28 publications

(18 citation statements)

References 38 publications

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“…CP‐25 has been reported to have therapeutic effects in rats with AA that are consistent with reductions in immune inflammation and bone damage by reducing inflammatory mediators and modulating immune responses . Previous studies have suggested that CP‐25 can regulate dendritic cell (DC) function and inhibit DC maturation in vitro , which could be relevant for the regulatory effects of CP‐25 on the PGE2 and TNF‐α signalling pathways . In the present study, we demonstrated for the first time that CP‐25 is a novel ester derivative of Pae that has therapeutic effects in a model of SS‐like diseases in NOD/Ltj mice.…”

Section: Discussionsupporting

confidence: 69%

CP‐25 Alleviates Experimental Sjögren's Syndrome Features in NOD/Ltj Mice and Modulates T Lymphocyte Subsets

Zhang

et al. 2018

Basic Clin Pharma Tox

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Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune illness of the moisture-producing glands such as salivary glands that is characterized by various immune abnormalities. The aetiology of pSS remains unclear and there is no curative agent. In this study, we investigated the putative therapeutic effects on a NOD/Ltj mouse model of Sjögren's syndrome-like disorders of an ester derivative of paeoniflorin, paeoniflorin-6'O-benzene (termed CP-25). Our study showed that CP-25 alleviated effectively clinical manifestations in NOD/Ltj mice resulting, for example, in increased salivary flow and reduced histopathological scores. Furthermore, CP-25 decreased lymphocyte viability in NOD/Ltj mice and attenuated the infiltration of Th1 cells and Th2 cells into the salivary glands of NOD/Ltj mice. In the spleen on NOD/Ltj mice, CP-25 skewed the ratio of Th17 and regulatory T cells towards regulatory T cells. After treatment, concentrations of anti-La/SSB and IgG antibodies were reduced and the titre of the inflammatory cytokines IFN-γ, IL-4, IL-6 and IL-17A in the serum on NOD/Ltj mice was alleviated. Thus, we define CP-25 as a novel compound that is a potent therapeutic agent for pSS by modulating T lymphocyte subsets. Future studies will validate the use of CP-25 as a therapeutic strategy for the treatment of pSS.

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Section: Discussionsupporting

confidence: 69%

CP‐25 Alleviates Experimental Sjögren's Syndrome Features in NOD/Ltj Mice and Modulates T Lymphocyte Subsets

Zhang

et al. 2018

Basic Clin Pharma Tox

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“…In addition, CP-25 showed superior intestinal absorption compared with Pae 27 . In vitro studies suggested that CP-25 regulates dendritic cell (DC) function and inhibits DC maturation via prostaglandin (PG) E2 and TNF-α signaling 28 . However, the therapeutic effects and anti-arthritic mechanism of CP-25 remain unclear compared with those of Pae and TGP.…”

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confidence: 99%

CP-25, a novel compound, protects against autoimmune arthritis by modulating immune mediators of inflammation and bone damage

Cao

Jia

Fang

et al. 2016

Sci Rep

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Paeoniflorin-6′-O-benzene sulfonate (code: CP-25), a novel ester derivative of paeoniflorin (Pae), was evaluated in rats with adjuvant-induced arthritis (AA) to study its potential anti-arthritic activity. AA rats were treated with CP-25 (25, 50, or 100 mg/kg) from days 17 to 29 after immunization. CP-25 effectively reduced clinical and histopathological scores compared with the AA groups. CP-25-treated rats exhibited decreases in pro-inflammatory cytokines (IL-1β, IL-6, IL-17 and TNF-α) coupled with an increase in the anti-inflammatory cytokine TGF-β1 in the serum. CP-25 treatment inhibited M1 macrophage activation and enhanced M2 macrophage activation by influencing cytokine production. Decreases in Th17-IL-17 and the Th17-associated transcription factor RAR-related orphan receptor gamma (ROR-γt) dramatically demonstrated the immunomodulatory effects of CP-25 on abnormal immune dysfunction. In addition, CP-25 suppressed the production of receptor activator of nuclear factor kappa B ligand (RANKL) and matrix metalloproteinase (MMP) 9, which supported its anti-osteoclastic effects. The data presented here demonstrated that CP-25 significantly inhibited the progression of rat AA by reducing inflammation, immunity and bone damage. The protective effects of CP-25 in AA highlight its potential as an ideal new anti-arthritic agent for human RA.

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“…The previous studies in our laboratory demonstrated that CP-25 significantly inhibited the progression of adjuvant arthritis rats by reducing inflammation, immunity, and bone damage primarily by modulating inflammatory mediators and immune responses, particularly Th17-IL-17 and CP-25 might repress the cell culture growth and cytokine secretion ability of fibroblast synovial cells (FLSs), and its inhibitory effects might be associated with its ability to inhibit the expression of BAFF-R in CD4 + T cells in a co-culture ( Chang et al, 2016 ; Jia et al, 2016 ). At the same time, our team also found that CP-25 could inhibit the maturation of dendritic cells stimulated by TNF-alpha or Prostaglandin E2 (PGE2) through down-regulating the expression of MHC-II, CD40, CD80, CD83, and CD86 ( Li et al, 2015 ), which suggested that CP-25 could regulate the function of immune cells. Therefore, some hypothesis are proposed.…”

Section: Introductionmentioning

confidence: 87%

CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents

et al. 2017

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Paeoniflorin-6′-O-benzene sulfonate (code: CP-25) was the chemistry structural modifications of Paeoniflorin (Pae). CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF) or Tumor necrosis factor alpha (TNF-alpha). CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19+ B cells, CD19+CD20+ B cells, CD19+CD27+ B cells and CD19+CD20+CD27+ B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

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Regulation of PGE2 signaling pathways and TNF-alpha signaling pathways on the function of bone marrow-derived dendritic cells and the effects of CP-25

Cited by 28 publications

References 38 publications

CP‐25 Alleviates Experimental Sjögren's Syndrome Features in NOD/Ltj Mice and Modulates T Lymphocyte Subsets

CP‐25 Alleviates Experimental Sjögren's Syndrome Features in NOD/Ltj Mice and Modulates T Lymphocyte Subsets

CP-25, a novel compound, protects against autoimmune arthritis by modulating immune mediators of inflammation and bone damage

CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents

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