Objective： To investigate the expression of CD40 and CD40 ligand （CD4OL） on the surface of peripheral blood mononuclear cells（PBMCs） in asthmatic rats and the effect of anti-CD40L McAb on cytokines of PBMCs. Meth...Objective： To investigate the expression of CD40 and CD40 ligand （CD4OL） on the surface of peripheral blood mononuclear cells（PBMCs） in asthmatic rats and the effect of anti-CD40L McAb on cytokines of PBMCs. Methods： Flow cytometry and RT-PCR were used to detect the expression of CD40 and CD40L of PBMCs in asthmatic rats. After the PBMCs was treated with anti-CD40L McAb, ELISA was used to detect the IL-4 and IFN-γ levels of culture supernatants. Results： Compared with the normal control group, the expression of CD40 and CD40L of PBMCs in asthmatic rats increased （P 〈 0.05）. Compared with the untreated group, the level of IL-γ and the ratio of IL-4/IFN-γ decreased after the PBMCs was treated with anti-CD40L McAb（P 〈 0.05）. Conclusion： The expression of CD40 and CD40L on the surface of PBMCs in asthmatic rats was up-regulated. Anti-CD40L McAb can rectify the imbalance of Th1 and Th2 cytokines.展开更多
Hepatitis C virus(HCV) has a high propensity to establish chronic infections. Failure of HCV-infected individuals to activate effective antiviral immune responses is at least in part related to HCV-induced impairment ...Hepatitis C virus(HCV) has a high propensity to establish chronic infections. Failure of HCV-infected individuals to activate effective antiviral immune responses is at least in part related to HCV-induced impairment of dendritic cells(DCs) that play a central role in activating T cell responses. Although the impact of HCV on DC phenotype and function is likely to be more prominent in the liver, major HCV-induced alterations are detectable in peripheral blood DCs(pb DCs) that represent the most accessible source of DCs. These alterations include numerical reduction, impaired production of inflammatory cytokines and increased production of immunosuppressive IL10. These changes in DCs are relevant to our understanding the immune mechanisms underlying the propensity of HCV to establish persistent infection. Importantly, the noninvasive accessibility of pb DCs renders the analysis of these cells a convenient procedure that can be serially repeated in patient follow-up. Accordingly, the study of pb DCs in HCV-infected patients during conventional treatment with pegylated interferon and ribavirin indicated that restoration of normal plasmacytoid DC count may represent an additional mechanism contributing to the efficacy of the dual therapy. It also identified the pre-treatment levels of plasmacytoid DCs and IL10 as putative predictors of response to therapy. Treatment of chronic HCV infection is changing, as new generation direct-acting antiviral agents will soon be available for use in interferon-free therapeutic strategies. The phenotypic and functional analysis of pb DCs in this novel therapeutic setting will provide a valuable tool for investigating mechanisms underlying treatment efficacy and for identifying predictors of treatment response.展开更多
Background: Bronchial asthma patients may develop various asthmatic response types to bronchial challenge with allergen, such as immediate (IAR), late (LAR), dual (DAR) or delayed (DYAR), due to different immunologic ...Background: Bronchial asthma patients may develop various asthmatic response types to bronchial challenge with allergen, such as immediate (IAR), late (LAR), dual (DAR) or delayed (DYAR), due to different immunologic mechanisms. The DYAR, beginning between 26-32 hrs and lasting up to 56 hrs after the allergen challenge, differs from the IAR, LAR and DAR in clinical, diagnostic and immunologic aspects. The aim of this study was to investigate the concentrations of the particular intracellular cytokines released by blood cells stimulated with relevant allergens “in vitro”, before and during the DYAR. Methods: In 23 patients, the repeated DYAR (p < 0.001) was supplemented with cytokine determination in the supernatants of the blood cells stimulated with relevant allergens before and up to 72 hours after the bronchial challenge, by means of enzyme-linked immunoassay. Results: The significantly elevated pre-challenge concentrations (p < 0.05) of IL-2, IL-17, IFN-γ and G-CSF released by allergen-stimulated blood cells “in vitro” were recorded in the DYAR patients as compared with healthy controls. The significantly increased post-challenge concentrations (p β, IL-2, IL-8, IL-12p70, IL-18, IFN-γ and TNF-α, whereas decreased concentrations of IL-4, IL-6 and IL-17, were released by blood cells stimulated with relevant allergens “in vitro”, as compared both with their pre-challenge concentrations and with the corresponding PBS control values. Conclusions: The profiles of cytokines released by allergen-stimulated peripheral blood cells during the DYAR would suggest an activation of Th1 cells, neutrophils, monocytes and probably also bronchial macrophages, epithelial and endothelial cells and their involvement in the immunologic mechanism(s) underlying the clinical DYAR.展开更多
AIM： To investigate the correlation between in vitro and in vivo immunomodulation potential of the probiotic strain and its ability to prevent experimental colitis in mice. METHODS： In vitro immunomodulation was ass...AIM： To investigate the correlation between in vitro and in vivo immunomodulation potential of the probiotic strain and its ability to prevent experimental colitis in mice. METHODS： In vitro immunomodulation was assessed by measuring interleukJn （IL）-12p70, IL-10, tumor necrosis factor alpha （TNFα） and interferon 7 （IFNγ） release by human peripheral blood mononuclear cells （PBMCs） after 24 h stimulation with 13 live bacterial strains. A murine model of acute TNBS-colitis was next used to evaluate the prophylactic protective capacity of the same set of strains. RESULTS： A strain-specific in vivo protection was observed. The strains displaying an in vitro potential to induce higher levels of the anti-inflammatory cytokine IL-10 and lower levels of the inflammatory cytokine IL-12, offered the best protection in the in vivo colitis model. In contrast, strains leading to a low IL-10/IU12 cytokine ratio could not significantly attenuate colitis symptoms, CONCLUSION：These results show that we could predict the in vivo protective capacity of the studied lactic acid bacteria （LAB） based on the cytokine profile we established in vitro. The PBHC-based assay we used may thus serve as a useful primary indicator to narrow down the number of candidate strains to be tested in murine models for their anti-inflammatory potential.展开更多
Long gap peripheral nerve injuries usually reulting in life-changing problems for patients. Skeletal muscle derived-multipotent stem cells （Sk-MSCs） can differentiate into Schwann and perineurial/endoneurial cells, ...Long gap peripheral nerve injuries usually reulting in life-changing problems for patients. Skeletal muscle derived-multipotent stem cells （Sk-MSCs） can differentiate into Schwann and perineurial/endoneurial cells, vascular relating pericytes, and endothelial and smooth muscle cells in the damaged peripheral nerve niche. Application of the Sk-MSCs in the bridging conduit for repairing long nerve gap injury resulted favorable axonal regeneration, which showing superior effects than gold standard therapy--healthy nerve autograft. This means that it does not need to sacrifice of healthy nerves or loss of related functions for repairing peripheral nerve injury.展开更多
The link between chronic inflammation and colorectal cancer has been well established. The events proceeding along tumorigenesis are complicated and involve cells activated at the cancer microenvironment, tumor infilt...The link between chronic inflammation and colorectal cancer has been well established. The events proceeding along tumorigenesis are complicated and involve cells activated at the cancer microenvironment, tumor infiltrating polymorphonuclears, immune cells including lymphocyte subtypes and peripheral blood mononuclear cells(PBMC), as well as tumor-associated macrophages. The immune cells generate inflammatory cytokines, several of them playing a crucial role in tumorigenesis. Additional factors, such as gene expression regulated by cytokines, assembling of tumor growth- and transforming factors, accelerated angiogenesis, delayed apoptosis, contribute all to initiation, development and migration of tumor cells. Oxygen radical species originating from the inflammatory area promote cell mutation and cancer proliferation. Tumor cells may over-express pro-inflammatory mediators that in turn activate immune cells for inflammatory cytokines production. Consequently, an immune dialogue emerges between immune and cancer cells orchestrated through a number of activated molecular pathways. Cytokines, encompassing migration inhibitory factor, transforming growth factor beta 1, tumor necrosisfactor-α, Interleukin(IL)-6, IL-10, IL-12, IL-17, IL-23 have been reported to be involved in human cancer development. Some cytokines, namely IL-5, IL-6, IL-10, IL-22 and growth factors promote tumor development and metastasis, and inhibit apoptosis via activation of signal transducer activator transcription-3 transcription factor. Colon cancer environment comprises mesenchymal, endothelial and immune cells. Assessment of the interaction between components in the tumor environment and malignant cells requires a reconsideration of a few topics elucidating the role of chronic inflammation in carcinogenesis, the function of the immune cells expressed by inflammatory cytokine production, the immunomodulation of cancer cells and the existence of a cross-talk between immune and malignant cells leading to a balance in cytokine production. It is conceivable that the prevalence of anti-inflammatory cytokine production by PBMC in the affected colonic mucosa will contribute to the delay, or even to halt down malignant expansion. Targeting the interplay between immune and cancer cells by mediators capable to alter cytokine secretion toward increased anti-inflammatory cytokine release by PBMC and tumor associated macrophages, may serve as an additional strategy for treatment of malignant diseases. This review will focus on the inflammatory events preceding tumorigenesis in general, and on a number of modulators capable to affect colon cancer cell-induced production of inflammatory cytokines by PBMC through alteration of the immune crosstalk between PBMC and cancer cells.展开更多
文摘Objective： To investigate the expression of CD40 and CD40 ligand （CD4OL） on the surface of peripheral blood mononuclear cells（PBMCs） in asthmatic rats and the effect of anti-CD40L McAb on cytokines of PBMCs. Methods： Flow cytometry and RT-PCR were used to detect the expression of CD40 and CD40L of PBMCs in asthmatic rats. After the PBMCs was treated with anti-CD40L McAb, ELISA was used to detect the IL-4 and IFN-γ levels of culture supernatants. Results： Compared with the normal control group, the expression of CD40 and CD40L of PBMCs in asthmatic rats increased （P 〈 0.05）. Compared with the untreated group, the level of IL-γ and the ratio of IL-4/IFN-γ decreased after the PBMCs was treated with anti-CD40L McAb（P 〈 0.05）. Conclusion： The expression of CD40 and CD40L on the surface of PBMCs in asthmatic rats was up-regulated. Anti-CD40L McAb can rectify the imbalance of Th1 and Th2 cytokines.
文摘Hepatitis C virus(HCV) has a high propensity to establish chronic infections. Failure of HCV-infected individuals to activate effective antiviral immune responses is at least in part related to HCV-induced impairment of dendritic cells(DCs) that play a central role in activating T cell responses. Although the impact of HCV on DC phenotype and function is likely to be more prominent in the liver, major HCV-induced alterations are detectable in peripheral blood DCs(pb DCs) that represent the most accessible source of DCs. These alterations include numerical reduction, impaired production of inflammatory cytokines and increased production of immunosuppressive IL10. These changes in DCs are relevant to our understanding the immune mechanisms underlying the propensity of HCV to establish persistent infection. Importantly, the noninvasive accessibility of pb DCs renders the analysis of these cells a convenient procedure that can be serially repeated in patient follow-up. Accordingly, the study of pb DCs in HCV-infected patients during conventional treatment with pegylated interferon and ribavirin indicated that restoration of normal plasmacytoid DC count may represent an additional mechanism contributing to the efficacy of the dual therapy. It also identified the pre-treatment levels of plasmacytoid DCs and IL10 as putative predictors of response to therapy. Treatment of chronic HCV infection is changing, as new generation direct-acting antiviral agents will soon be available for use in interferon-free therapeutic strategies. The phenotypic and functional analysis of pb DCs in this novel therapeutic setting will provide a valuable tool for investigating mechanisms underlying treatment efficacy and for identifying predictors of treatment response.
文摘Background: Bronchial asthma patients may develop various asthmatic response types to bronchial challenge with allergen, such as immediate (IAR), late (LAR), dual (DAR) or delayed (DYAR), due to different immunologic mechanisms. The DYAR, beginning between 26-32 hrs and lasting up to 56 hrs after the allergen challenge, differs from the IAR, LAR and DAR in clinical, diagnostic and immunologic aspects. The aim of this study was to investigate the concentrations of the particular intracellular cytokines released by blood cells stimulated with relevant allergens “in vitro”, before and during the DYAR. Methods: In 23 patients, the repeated DYAR (p < 0.001) was supplemented with cytokine determination in the supernatants of the blood cells stimulated with relevant allergens before and up to 72 hours after the bronchial challenge, by means of enzyme-linked immunoassay. Results: The significantly elevated pre-challenge concentrations (p < 0.05) of IL-2, IL-17, IFN-γ and G-CSF released by allergen-stimulated blood cells “in vitro” were recorded in the DYAR patients as compared with healthy controls. The significantly increased post-challenge concentrations (p β, IL-2, IL-8, IL-12p70, IL-18, IFN-γ and TNF-α, whereas decreased concentrations of IL-4, IL-6 and IL-17, were released by blood cells stimulated with relevant allergens “in vitro”, as compared both with their pre-challenge concentrations and with the corresponding PBS control values. Conclusions: The profiles of cytokines released by allergen-stimulated peripheral blood cells during the DYAR would suggest an activation of Th1 cells, neutrophils, monocytes and probably also bronchial macrophages, epithelial and endothelial cells and their involvement in the immunologic mechanism(s) underlying the clinical DYAR.
基金Supported by the EU granted QLK1-2000-00146 DEPROHEALTH research program, Institut Pasteur de Lille funding and funds from DANISCO France
文摘AIM： To investigate the correlation between in vitro and in vivo immunomodulation potential of the probiotic strain and its ability to prevent experimental colitis in mice. METHODS： In vitro immunomodulation was assessed by measuring interleukJn （IL）-12p70, IL-10, tumor necrosis factor alpha （TNFα） and interferon 7 （IFNγ） release by human peripheral blood mononuclear cells （PBMCs） after 24 h stimulation with 13 live bacterial strains. A murine model of acute TNBS-colitis was next used to evaluate the prophylactic protective capacity of the same set of strains. RESULTS： A strain-specific in vivo protection was observed. The strains displaying an in vitro potential to induce higher levels of the anti-inflammatory cytokine IL-10 and lower levels of the inflammatory cytokine IL-12, offered the best protection in the in vivo colitis model. In contrast, strains leading to a low IL-10/IU12 cytokine ratio could not significantly attenuate colitis symptoms, CONCLUSION：These results show that we could predict the in vivo protective capacity of the studied lactic acid bacteria （LAB） based on the cytokine profile we established in vitro. The PBHC-based assay we used may thus serve as a useful primary indicator to narrow down the number of candidate strains to be tested in murine models for their anti-inflammatory potential.
基金supported by a 2013 Tokai University School of Medicine,Project Research Grant
文摘Long gap peripheral nerve injuries usually reulting in life-changing problems for patients. Skeletal muscle derived-multipotent stem cells （Sk-MSCs） can differentiate into Schwann and perineurial/endoneurial cells, vascular relating pericytes, and endothelial and smooth muscle cells in the damaged peripheral nerve niche. Application of the Sk-MSCs in the bridging conduit for repairing long nerve gap injury resulted favorable axonal regeneration, which showing superior effects than gold standard therapy--healthy nerve autograft. This means that it does not need to sacrifice of healthy nerves or loss of related functions for repairing peripheral nerve injury.
文摘The link between chronic inflammation and colorectal cancer has been well established. The events proceeding along tumorigenesis are complicated and involve cells activated at the cancer microenvironment, tumor infiltrating polymorphonuclears, immune cells including lymphocyte subtypes and peripheral blood mononuclear cells(PBMC), as well as tumor-associated macrophages. The immune cells generate inflammatory cytokines, several of them playing a crucial role in tumorigenesis. Additional factors, such as gene expression regulated by cytokines, assembling of tumor growth- and transforming factors, accelerated angiogenesis, delayed apoptosis, contribute all to initiation, development and migration of tumor cells. Oxygen radical species originating from the inflammatory area promote cell mutation and cancer proliferation. Tumor cells may over-express pro-inflammatory mediators that in turn activate immune cells for inflammatory cytokines production. Consequently, an immune dialogue emerges between immune and cancer cells orchestrated through a number of activated molecular pathways. Cytokines, encompassing migration inhibitory factor, transforming growth factor beta 1, tumor necrosisfactor-α, Interleukin(IL)-6, IL-10, IL-12, IL-17, IL-23 have been reported to be involved in human cancer development. Some cytokines, namely IL-5, IL-6, IL-10, IL-22 and growth factors promote tumor development and metastasis, and inhibit apoptosis via activation of signal transducer activator transcription-3 transcription factor. Colon cancer environment comprises mesenchymal, endothelial and immune cells. Assessment of the interaction between components in the tumor environment and malignant cells requires a reconsideration of a few topics elucidating the role of chronic inflammation in carcinogenesis, the function of the immune cells expressed by inflammatory cytokine production, the immunomodulation of cancer cells and the existence of a cross-talk between immune and malignant cells leading to a balance in cytokine production. It is conceivable that the prevalence of anti-inflammatory cytokine production by PBMC in the affected colonic mucosa will contribute to the delay, or even to halt down malignant expansion. Targeting the interplay between immune and cancer cells by mediators capable to alter cytokine secretion toward increased anti-inflammatory cytokine release by PBMC and tumor associated macrophages, may serve as an additional strategy for treatment of malignant diseases. This review will focus on the inflammatory events preceding tumorigenesis in general, and on a number of modulators capable to affect colon cancer cell-induced production of inflammatory cytokines by PBMC through alteration of the immune crosstalk between PBMC and cancer cells.
