Sinomenine induces the generation of intestinal Treg cells and attenuates arthritis via activation of aryl hydrocarbon receptor

Tong, Bei; Yuan, Xusheng; Dou, Youjun; Wu, Xin; Wang, Yuhui; Xia, Yufeng; Dai, Yue

doi:10.1038/labinvest.2016.86

Cited by 32 publications

(21 citation statements)

References 30 publications

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“…Some evidence suggests that AhR activation increases Th17 cell differentiation and the secretion of IL-17A and IL-22 (Shinde and McGaha, 2018). However, the results obtained after treatment of the CIA model consistently suggested that activation of the AhR inhibits the differentiation and function of Th17 cells (Tong et al, 2015(Tong et al, , 2016b. This difference in results might be due to the type of ligand and animal species used and the disease type examined.…”

Section: Discussionmentioning

confidence: 98%

Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor

Lü

Fan

et al. 2020

Front. Cell Dev. Biol.

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Background: Rheumatoid arthritis (RA) is an autoimmune disease that may be associated with gut microbiota via the aryl hydrocarbon receptor (AhR). Human umbilical mesenchymal stem cells (HUMSCs) have therapeutic potential against RA, but the underlying mechanism has not been fully elucidated. The purpose of this study was to explore the mechanism of action of HUMSCs in rats with collagen-induced arthritis (CIA). Method: HUMSCs (1 × 10 6) were transplanted into each rat with CIA. The tissue localization of HUMSCs and the therapeutic effects in the ankles were assessed. The immune status and expression of immune-related genes and proteins in related lymphoid tissues were subsequently tested. Furthermore, the levels of immune-related factors in serum and the changes in gut microbiota in the ileum were detected, and the levels of indole and their derivatives in plasma and the levels of AhR in the ileum were evaluated. Results: HUMSCs homed to the popliteal lymph node (PLN), mesenteric lymph node (MLN), ankle cartilage, and ileum mucosa in rats with CIA. The transplantation of HUMSCs reduced the pathology scores and the degree of bone damage in the ankles. The immune status of T regulatory cells (Tregs) and T helper (Th)17 cells and the gene expression levels of interleukin (IL)-10, transforming growth factor (TGF)-β1, and IL-17A were altered in the PLN, which is the lymph tissue closest to the nidus, and the MLN, which is one of the gut-associated lymphoid tissues (GALTs). The proportion and function of B cells, Tregs, and Th17 cells were regulated in other GALTs, namely,

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Section: Discussionmentioning

confidence: 98%

Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor

Lü

Fan

et al. 2020

Front. Cell Dev. Biol.

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“…Arthritis was induced in rats by immunization with an emulsion of chicken type II collagen (CII, Sigma-Aldrich Co., St. Louis, MO, USA) and complete Freund’s adjuvant (CFA, Becton Drive Co., NJ, USA) as previously reported [ 28 ]. Briefly, rats were intradermally injected with 200 μl of this emulsion at the base of the tail on day 0.…”

Section: Methodsmentioning

confidence: 99%

“…The right ankles were fixed in 10% buffered formalin for 48 h. The joints were then decalcified in 10% EDTA, embedded in paraffin, cut into 5-μm serial sections, and stained with hematoxylin and eosin (H&E). The histopathological changes in the joints were examined using an optical microscope and graded on a scale of 0–3 (0 = none changes, 1 = mild changes, 2 = moderate changes, and 3 = severe changes) by a pathologist blinded to the experimental groups [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

Curcumin attenuates collagen-induced inflammatory response through the “gut-brain axis”

Dou

Luo

et al. 2018

J Neuroinflammation

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BackgroundPrevious studies have demonstrated that oral administration of curcumin exhibited an anti-arthritic effect despite its poor bioavailability. The present study aimed to explore whether the gut-brain axis is involved in the therapeutic effect of curcumin.MethodsThe collagen-induced arthritis (CIA) rat model was induced by immunization with an emulsion of collagen II and complete Freund’s adjuvant. Sympathetic and parasympathetic tones were measured by electrocardiographic recordings. Unilateral cervical vagotomy (VGX) was performed before the induction of CIA. The ChAT, AChE activities, and serum cytokine levels were determined by ELISA. The expression of the high-affinity choline transporter 1 (CHT1), ChAT, and vesicular acetylcholine transporter (VAChT) were determined by real-time PCR and immunohistochemical staining. The neuronal excitability of the vagus nerve was determined by whole-cell patch clamp recording.ResultsOral administration of curcumin restored the imbalance between the sympathetic and parasympathetic tones in CIA rats and increased ChAT activity and expression of ChAT and VAChT in the gut, brain, and synovium. Additionally, VGX eliminated the effects of curcumin on arthritis and ACh biosynthesis and transport. Electrophysiological data showed that curcumin markedly increased neuronal excitability of the vagus nerve. Furthermore, selective α7 nAChR antagonists abolished the effects of curcumin on CIA.ConclusionsOur results demonstrate that curcumin attenuates CIA through the “gut-brain axis” by modulating the function of the cholinergic system. These findings provide a novel approach for mechanistic studies of anti-arthritic compounds with low oral absorption and bioavailability.

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“…Previous research examining the efficacy of BBR as a DSS-induced UC treatment, for example, reported that BBR improved the T reg /T h 17 balance [58]. One possible mechanism for our observed increase in the proportion of T reg is via AhR signaling; two studies involving the use of other alkaloids, sinomenine [59] and norisoboldine [60], ameliorated CIA and increased T reg populations in an AhR-dependent manner; BBR has also been shown to activate AhR [61][62][63]. Additionally, one study examining the protective effect of keratinocyte growth factor on CIA development reported that there were increased percentages of T reg in animals who experienced delayed onset [64], providing evidence for the protective role of T reg in delaying the onset of CIA.…”

Section: Discussionmentioning

confidence: 71%

Berberine delays onset of collagen induced arthritis through T cell suppression

Vita¹,

Lyons²,

Aljobaily³

et al. 2019

Preprint

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RUNNING TITLE (less than 50 characters): Berberine delays onset of collagen arthritis model KEY WORDS (5 words not in the title): CIA, berberine, RA, autoimmune, T cell ABSTRACT (250 words or less): Previous evidence suggests that berberine (BBR), a clinically relevant plant-derived alkaloid, alleviates symptoms of clinically apparent collagen induced arthritis (CIA), and may have a prophylactic role from in vitro studies. Thus, we used a CIA model to determine if BBR merits further exploration as a prophylactic treatment for rheumatoid arthritis. Mice were treated with either 1 mg/kg/day of BBR or a vehicle (PBS) control via IP injections from day 0 to day 28, were left untreated (CIA control), or were in a non-arthritic control group. Incidence of arthritis in BBR mice was 40%, compared to 90% in the CIA and 80% in the PBS controls. Populations of B cells and T cells from the spleens and draining lymph nodes were examined from mice across treatment groups on day 14 and from the remaining mice on day 28 when arthritic signs and symptoms were expected to be apparent. BBR-treated mice had significantly reduced populations of CD4 + T cells, CXCR5 + T fh cells, and an increased proportion of T reg at both day 14 and day 28 endpoints, as well as decreased CD28 + and CD154 + CD4 + T cells at day 14. BBR-treated mice also experienced a significant reduction of CD19 + B cells in LNs at day 28. Additionally, BBR treatment resulted in significantly lower anti-collagen type II-specific (anti-CII) IgG2a and anti-CII total IgG serum concentrations. These results indicate a potential role for BBR as a prophylactic supplement, and that its effect may be mediated through T cell suppression, which indirectly affects B cell activity. and PBS controls ( Fig. 2B). When comparing anti-CII IgG levels between arthritic and nonarthritic mice within the BBR group specifically, however, anti-CI IgG1, IgG2a and total IgG were all significantly reduced in the non-arthritic mice compared to those who developed arthritis (Fig. 2C). Additionally, there appeared to be a vehicle-specific effect on circulating anti-CII IgG in which the administration of PBS with 0.01% DMSO elicited elevated levels of anti-CII IgG1 and total IgG in vehicle control mice ( Fig. 2A-B).Key CD4 + T cell population characteristics in response to berberine treatment-On day 14, we observed a significant reduction in populations of both CD4 + T cells and CXCR5 + T fh cells in the LNs and spleen of BBR-treated mice (Fig. 3A-B), as well as a reduction in the percentage of CD28 + and CD154 + CD4 + T cells in the spleen and LNs of BBR-treated mice (Fig. 3A-B). By the day 28 experimental endpoint we continued to observe a significant reduction in CD4 + T cells and CXCR5 + T fh cells in the spleen and LNs of BBR-treated mice ( Fig. 3C-D), however, there was no significant difference in the percentage of CD28 + and CD154 + CD4 + T cells between treatment groups (Fig 3C-D). Berberine treatment leads to increased proportion of FOXP3 + CD25 + CD4 + T cells-To examineBBRs effect on ...

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Sinomenine induces the generation of intestinal Treg cells and attenuates arthritis via activation of aryl hydrocarbon receptor

Cited by 32 publications

References 30 publications

Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor

Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor

Curcumin attenuates collagen-induced inflammatory response through the “gut-brain axis”

Berberine delays onset of collagen induced arthritis through T cell suppression

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