Nocardia rubra cell-wall skeleton promotes CD4 + T cell activation and drives Th1 immune response

Wang, Guangchuan; Wu, Jie; Miao, Miao; Dou, Haoran; Ning, Ning; Shi, Mingsheng; Yu, Guang; Shan, Fengping

doi:10.1016/j.ijbiomac.2017.03.060

Cited by 15 publications

(23 citation statements)

References 22 publications

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“…The possible mechanism involves Nr‐CWS reducing the expression levels of PD‐L1 and attenuating the immunosuppression. Based on these results, we hypothesize that Nr‐CWS enhances the antitumor effect of dendritic cells and macrophages 15,16 …”

Section: Discussionmentioning

confidence: 86%

“…Nr‐CWS can significantly promote the activity of Cytokine‐Induced Killer cells, DCs and Natural Killer cells, which exert strong antitumor activity especially by inducing apoptosis 14 . In addition, Nr‐CWS increases the response of CD8+T cell and activation of CD4+T cell, and promotes the differentiation of CD4+T cells into Th1 cells 15,16 . Ct26.WT tumor‐bearing mice were injected with Nr‐CWS and PD‐1 inhibitors simultaneously, which significantly inhibited the growth of transplanted tumor.…”

Section: Introductionmentioning

confidence: 99%

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Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

et al. 2022

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Background As an immune enhancer, Nocardia rubra cell‐wall skeleton (Nr‐CWS) has been used to treat persistent human papillomavirus infection and cervical precancerous lesions. However, it is still unclear whether it can be used to treat cervical carcinoma. Methods In our study, the aim was to determine whether Nr‐CWS affects the apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages in vivo and in vitro. Results The experimental results showed that Nr‐CWS can promote the activity of dendritic cells and macrophages and reduce their apoptosis. It also increased the cytokines IL‐6, IL‐12, TNF‐ɑ, and IL‐1β secreted by dendritic cells and macrophages and reduced their PD‐L1 expression. In vitro, Nr‐CWS inhibited the proliferation, colony forming ability of HeLa and SiHa cervical carcinoma cell lines cultured with macrophages, and more cells were blocked in G2/M phase. Nr‐CWS promoted TNF‐ɑ/TNFR1/caspase‐8‐mediated apoptosis by increasing macrophages secretion of TNF‐ɑ and inhibited cell migration and invasion regulated by the WNT/β‐catenin‐EMT pathway. Nr‐CWS also reduced the expression of the cervical carcinoma genes E6 and E7 thereby increasing expression of p53 gene and decreasing expression of PD‐L1 gene. In vivo, Nr‐CWS inhibited tumor growth and decreased the expression of E6, E7, PD‐L1, P16, Ki67, and PCNA in tumors. Conclusions Therefore, our results suggest that Nr‐CWS can promote apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages.

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Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

et al. 2022

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“…Nr-CWS was first reported by Azuma et al in 1976 (9) and was subsequently shown to exert antitumor effects and affect the complex immune network formed by interactions of immunocompetent cells (10). Recently, it has been proved in vitro that Nr-CWS could stimulate macrophages (11), dendritic cells, natural killer cells (12), CD4 + T cells (13), and CD8 + T cells (14), which imply its potential application in immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Nocardia Rubra Cell Wall Skeleton Up-Regulates T Cell Subsets and Inhibits PD-1/PD-L1 Pathway to Promote Local Immune Status of Patients With High-Risk Human Papillomavirus Infection and Cervical Intraepithelial Neoplasia

Chen

Zhang²,

Zhao

et al. 2021

Front. Immunol.

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The Nocardia rubra cell wall skeleton (Nr-CWS) for external use is an immune enhancer, which has been widely used in human cervix diseases such as cervical erosion, but the mechanism of Nr-CWS enhancing immunity is still unclear. The purpose of this study was to explore the effect and mechanism of Nr-CWS on the local immune status of cervical tissue in patients with high-risk human papillomavirus (HR-HPV) infection and cervical precancerous lesion, cervical intraepithelial neoplasia (CIN). The recruited patients with HR-HPV infection and CIN were treated with Nr-CWS. The specimens were taken from these patients before and after local application of Nr-CWS respectively. The normal control specimens were tested simultaneously. Serial section analysis of immunohistochemistry and co-expression analysis were performed to characterize populations of T cells and the expressions of programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1). The levels of cytokines in local cervical tissue were also detected. Nr-CWS significantly increased T cells including CD4+, CD8+ T cells, and reduced the expression of PD-L1 in the patients’ local cervical tissues. Co-expression analyses showed that the proportions of PD-1+CD4+ cells in CD4+ T cells and PD-1+CD8+ cells in CD8+ T cells decreased after Nr-CWS application. Furthermore, the increase in the number of immune cells was accompanied by increased pro-inflammatory cytokines interleukin-12 (IL-12), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and decreased suppressive cytokine IL-10. The results indicate that Nr-CWS, as an immunotherapeutic agent for HR-HPV infection and CIN, plays an immune promoting role related to the upregulation of T cell subsets and the inhibition of PD-1/PD-L1 pathway.

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“… 12 Some species can cause multiple illnesses, including an invasive disease known as nocardiosis. N-CWS is composed of lipids (17.1%), polysaccharides (46.3%), and peptidoglycans (36.4%) 13 and exhibits immunoregulatory and antitumor effects. 5 , 13 – 15 In the present study, a full-thickness wound was excised on the back of rats.…”

Section: Discussionmentioning

confidence: 99%

“…N-CWS is composed of lipids (17.1%), polysaccharides (46.3%), and peptidoglycans (36.4%) 13 and exhibits immunoregulatory and antitumor effects. 5,[13][14][15] In the present study, a full-thickness wound was excised on the back of rats. N-CWS was found to significantly accelerate cutaneous wound healing.…”

Section: Discussionmentioning

confidence: 99%

Nocardia rubra cell wall skeleton accelerates cutaneous wound healing by enhancing macrophage activation and angiogenesis

Wang

et al. 2018

J Int Med Res

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ObjectiveThis study was performed to investigate the effect of Nocardia rubra cell wall skeleton (N-CWS) on wound healing of full-thickness skin defects.MethodsTwo 2- × 2-cm full-thickness wounds, one on each side of the midline, were made on the back of 12 rats. One wound was covered with Vaseline gauze soaked in normal saline, whereas the other was covered with Vaseline gauze and N-CWS. Wound dressings were changed every other day from day 0 (wound creation) to day 11. Four of the 12 rats were killed on day 7, and biopsy samples were obtained for biochemical and histopathological analyses. The expression levels of CD31, CD68, and F4/80 in the tissues were examined immunohistologically. The expression of transforming growth factor (TGF)-β1 in the wound was determined by western blot.ResultsN-CWS increased the wound healing rate, reduced the complete wound healing time, and increased the expression levels of CD31, CD68, and F4/80 on day 7. The TGF-β1 expression level in the wound was significantly higher in the N-CWS group than in the control group on day 7.ConclusionsN-CWS can activate macrophages, increase TGF-β1 expression, and enhance angiogenesis and thus accelerate cutaneous wound healing.

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Nocardia rubra cell-wall skeleton promotes CD4 + T cell activation and drives Th1 immune response

Cited by 15 publications

References 22 publications

Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

Nocardia Rubra Cell Wall Skeleton Up-Regulates T Cell Subsets and Inhibits PD-1/PD-L1 Pathway to Promote Local Immune Status of Patients With High-Risk Human Papillomavirus Infection and Cervical Intraepithelial Neoplasia

Nocardia rubra cell wall skeleton accelerates cutaneous wound healing by enhancing macrophage activation and angiogenesis

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