Polysaccharopeptide mimics ciclosporin-mediated Th1/Th2 cytokine balance for suppression of activated human T cell proliferation by MAPKp38 and STAT5 pathways

Lee, Cheuk‐Lun; Sit, Wai-Hung; Jiang, Pingping; So, Ivy Wing-Yan; Wan, Jennifer Man-Fan

doi:10.1211/jpp/60.11.0010

Cited by 7 publications

(6 citation statements)

References 38 publications

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“…Ho et al found that PSP promotes the proliferation of mouse splenic lymphocytes and increases the expression of Th1 cellassociated cytokines, including IL-2, IL-12, IFN-γ and IL-18, in mouse splenic lymphocytes in vitro (30). An additional study showed that PSP exhibited suppressive effects on Th1 cytokines, including IL-2, but stimulated the production of the Th2 cytokine, IL-10, to inhibit T-cell proliferation in human PBMCs in vitro (31). The effect of PSP on the Th1/Th2 balance is controversial.…”

Section: A B C D E Fmentioning

confidence: 99%

Immunomodulatory effects of polysaccharopeptide in immunosuppressed mice induced by cyclophosphamide

Huang

Zhang

Liu

et al. 2013

Molecular Medicine Reports

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Polysaccharopeptide (PSP) is well known for its immunoregulatory effects. In the present study, the effect of PSP on white blood cell (WBC) count, T lymphocyte subsets, B lymphocytes, Th1/Th2 balance and negative immune regulators was investigated using an immunosuppressed mouse model. The results demonstrated that the WBC count and the absolute number of CD3+CD4+ T cells, CD3+CD8+ T cells and CD3‑CD19+ B cells in the peripheral blood were increased in PSP‑treated groups as compared with the cyclophosphamide (Cy) group. In addition, PSP reduced interleukin (IL)‑4 and GATA binding protein 3 (GATA‑3) mRNA relative expression levels and elevated the ratios of IL‑2/IL‑4 and the transcription factors, T‑box‑containing protein/GATA‑3. The relative mRNA expression levels of the forkhead/winged‑helix transcription factor box protein 3 (Foxp3), programmed death‑1 (PD‑1) and IL‑10 were also downregulated by PSP. These observations indicate that the immunoregulatory effects of PSP are associated with restoration of WBC number, improving the absolute number of T lymphocyte subsets and B lymphocytes, inducing the Th1/Th2 response and downregulating the negative immune regulators, Foxp3, PD‑1 and IL‑10.

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Section: A B C D E Fmentioning

confidence: 99%

Immunomodulatory effects of polysaccharopeptide in immunosuppressed mice induced by cyclophosphamide

Huang

Zhang

Liu

et al. 2013

Molecular Medicine Reports

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“…Polysaccharopeptide (PSP), a medicinal microbial metabolite derived from Coriolus versicolor , is known to be a modifier of the biological response via its ability to exert regulatory effects on the immune system [10,11,13,17,18] . In this study, we investigated the regulatory mechanisms of PSP on lymphocyte homoeostasis and compared its activity with that of ciclosporin.…”

Section: Discussionmentioning

confidence: 99%

“…In search of immunomodulatory agents with adjuvant potential with ciclosporin, our previous studies showed that polysaccharopeptide (PSP) derived from a Chinese medicinal fungus, Coriolus versicolor , possessed similar immunomodulatory mechanisms as ciclosporin in modulating human lymphocytes responses [10,11] . PSP is a proteoglycan of approximately 100 kDa produced from the mycelia of the fungus by fermentation technology [12] .…”

Section: Introductionmentioning

confidence: 99%

“…PSP is well‐known for its anticancer, anti‐inflammatory, immunoregulatory and antiviral effects, attaining widespread usage as an immunomodifier in both healthy and cancerous individuals in many Asian countries [13–16] . PSP exhibits mechanistic actions similar to ciclosporin in the control of lymphocytic Th1 and Th2 cytokines by suppression of the MAPKp38 and STAT5 pathways [11] . Proteomic analysis has also revealed that the two medical fungal extracts share certain regulatory proteins in controlling lymphocyte activity [10] .…”

Section: Introductionmentioning

confidence: 99%

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Immunomodulatory properties of polysaccharopeptide derived from Coriolus versicolor and its combined effect with Cyclosporine a in activated human T-cells

Lee¹,

李卓倫.²

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Objectives Lymphocyte homoeostasis is essential in inflammatory and autoimmune diseases. In search of natural fungal metabolites with effects on lymphocyte homoeostasis, we recently reported that polysaccharopeptide (PSP) from Coriolus versicolor exhibited ciclosporin‐like activity in controlling aberrant lymphocyte activation. This object of this study was to investigate its effect on lymphocyte homoeostasis. This was done by investigating the mechanistic actions of PSP in relation to ciclosporin by performing cell cycle and cell death analysis of human lymphocytes in vitro. Methods We investigated the effect of PSP in the presence and absence of ciclosporin on cell proliferation, cell cycle, cell death, immunophenotype and cell cycle regulatory proteins in human lymphocytes. Key findings The data showed that PSP exhibited homoeostatic activity by promoting and inhibiting the proliferation of resting and phytohaemagglutinin (PHA)‐stimulated lymphocytes, respectively. PHA‐stimulated lymphocytes exhibited G0/G1 cell cycle arrest that was accompanied by a reduction of cyclin E expression with PSP treatment. Both PSP and ciclosporin blocked the reduction of the CD4/CD8 ratio in stimulated lymphocytes. PSP did not induce cell death in human lymphocytes, but the suppression of the Fasreceptor suggested a protective role of PSP against extrinsic cell death signals. These homoeostatic effects were more potent with combined PSP and ciclosporin treatment than with either fungal metabolite alone. Conclusions Collectively, the results reveal certain novel effects of PSP in lymphocyte homoeostasis and suggest potential as a specific immunomodulatory adjuvant for clinical applications in the treatment of autoimmune diseases.

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“…Fungus-derived natural products and their derivatives, such as cyclosporine and mycophenolate mofetil, are widely used in the treatment of autoimmune diseases (Lee et al , 2008;Fakih et al , 2018). Preparations of fungi and their metabolites have a low synthetic cost, high practical value, and broad application in medicine, thanks to their wide availability and high biological activity (Sharma et al , 2016).…”

Section: Introductionmentioning

confidence: 99%

Secoemestrin C inhibits activation of NKT/conventional T cells and protects against concanavalin A-induced autoimmune hepatitis in mice

et al.

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Background and Purpose: We previously found that secoemestrin C, an epitetrathiodioxopiperazine isolated from Aspergillus nidulans, has a potent immunosuppressive effect on splenocyte proliferation in drug screening. Here, we determined the immunomodulatory and hepatoprotective effects of secoemestrin C in a mouse model of acute autoimmune hepatitis. Experimental Approach: In an in vitro assay, purified hepatic mononuclear cells (MNCs) from C57BL/6J mice were stimulated with concanavalin A (Con A, 2 μg•mL-1) in the presence of secoemestrin C, and cell proliferation and cytokine production were measured. In an in vivo assay, mice with or without secoemestrin C pretreatment were injected with Con A (12 mg•kg-1) to induce acute hepatitis. Blood samples and liver tissues were harvested 8 h after Con A injection. Liver injury, serum levels of proinflammatory cytokines, hepatic lymphocyte subset ratios, and the functional status of NKT and conventional T cells were analyzed. Key Results: Secoemestrin C treatment dose-dependently suppressed cell proliferation and proinflammatory cytokine secretion in Con A-stimulated hepatic MNCs in vitro. In Con A-challenged mice, pre-injection with secoemestrin C significantly decreased the generation of proinflammatory cytokines and ameliorated liver injury. Furthermore, pretreatment with secoemestrin C significantly inhibited the Con A-induced activation of NKT and conventional T cells and decreased the production of IFN-γ by these two cell populations. Conclusion and Implications: Secoemestrin C has an immunosuppressive effect on NKT and conventional T cells and has hepatoprotective activity in mouse autoimmune hepatitis. These findings provide new insights into the use of fungus-derived natural products for the treatment of autoimmune diseases.

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Polysaccharopeptide mimics ciclosporin-mediated Th1/Th2 cytokine balance for suppression of activated human T cell proliferation by MAPKp38 and STAT5 pathways

Cited by 7 publications

References 38 publications

Immunomodulatory effects of polysaccharopeptide in immunosuppressed mice induced by cyclophosphamide

Immunomodulatory effects of polysaccharopeptide in immunosuppressed mice induced by cyclophosphamide

Immunomodulatory properties of polysaccharopeptide derived from Coriolus versicolor and its combined effect with Cyclosporine a in activated human T-cells

Secoemestrin C inhibits activation of NKT/conventional T cells and protects against concanavalin A-induced autoimmune hepatitis in mice

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