目的探讨腺苷对股动脉狭窄远端腺苷A2b受体表达与血清一氧化氮(NO)浓度的影响。方法取40只 Wistar 大鼠,对其中20只大鼠进行结扎股动脉术制备狭窄模型后,随机分为模型生理盐水组(A组)、模型腺苷组(B组),剩余20只大鼠只进行股动静脉分离...目的探讨腺苷对股动脉狭窄远端腺苷A2b受体表达与血清一氧化氮(NO)浓度的影响。方法取40只 Wistar 大鼠,对其中20只大鼠进行结扎股动脉术制备狭窄模型后,随机分为模型生理盐水组(A组)、模型腺苷组(B组),剩余20只大鼠只进行股动静脉分离,并随机分为对照生理盐水组(C组)和对照腺苷组(D组)。采用免疫组化法检测股动脉远端腺苷A2b受体的表达,硝酸还原酶法检测血清中NO的含量。结果免疫组化结果,B组的腺苷A2b受体阳性率低于D组( P <0.05),且D组高于A、C两组。硝酸还原酶法结果,B组NO在血清中含量远低于D组( P <0.01),且D组高于A、C两组。结论腺苷可致股动脉狭窄远端腺苷A2b受体表达和NO的浓度明显降低。展开更多
Tolerogenic dendritic cells(tol DCs)facilitate the suppression of autoimmune responses by differentiating regulatory T cells(Treg).The dysfunction of immunotolerance results in the development of autoimmune diseases,s...Tolerogenic dendritic cells(tol DCs)facilitate the suppression of autoimmune responses by differentiating regulatory T cells(Treg).The dysfunction of immunotolerance results in the development of autoimmune diseases,such as rheumatoid arthritis(RA).As multipotent progenitor cells,mesenchymal stem cells(MSCs),can regulate dendritic cells(DCs)to restore their immunosuppressive function and prevent disease development.However,the underlying mechanisms of MSCs in regulating DCs still need to be better defined.Simultaneously,the delivery system for MSCs also influences their function.Herein,MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ,maximizing efficacy in vivo.The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines.In the collagen-induced arthritis(CIA)mice model,alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39^(+)CD73^(+)on MSCs.These enzymes hydrolyze ATP to adenosine and activate A_(2A/2B)receptors on immature DCs,further promoting the phenotypic transformation of DCs to tol DCs and regulating naive T cells to Tregs.Therefore,encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression.This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.展开更多
Adenosine receptors are a family of G-coupled receptors which mediate the anti-inflammatory and immune-suppressive effects of adenosine in a damaged tissue.A large number of evidence indicate that the accumulation of ...Adenosine receptors are a family of G-coupled receptors which mediate the anti-inflammatory and immune-suppressive effects of adenosine in a damaged tissue.A large number of evidence indicate that the accumulation of adenosine under hypoxic conditions favors tumor progression,helping cancer cells to evade immune responses.Tumor cells and/or lymphoid and myeloid cells can express the adenosine-generating enzyme CD73 and/or A2A receptor,which in turn strongly suppresses an effective T-cell-mediated response,while promotes the activity of suppressive cells such as Treg and myeloid-derived suppressor cells.CD73 inhibitors and A2A antagonists,either as single agents,or in combination with immune-checkpoints inhibitors such as anti PD-1 monoclonal antibodies,are currently in Phase I clinical trial in cancer patients.Recent studies show that A2B receptor plays an important role in mediating the pro-tumor effects of adenosine,since its selective blockade can inhibit tumor growth in some murine tumor models.Targeting A2B receptor reduces immunosuppression induced by myeloid cells and inhibits the stromal cells activity within the tumor microenvironment,limiting tumor angiogenesis and metastatic processes.Here,the authors review the current data on involvement of A2B receptor in regulating tumor progression and discuss the development of A2B receptor inhibitors as potential therapeutic agents in cancer treatment.展开更多
文摘目的探讨腺苷对股动脉狭窄远端腺苷A2b受体表达与血清一氧化氮(NO)浓度的影响。方法取40只 Wistar 大鼠,对其中20只大鼠进行结扎股动脉术制备狭窄模型后,随机分为模型生理盐水组(A组)、模型腺苷组(B组),剩余20只大鼠只进行股动静脉分离,并随机分为对照生理盐水组(C组)和对照腺苷组(D组)。采用免疫组化法检测股动脉远端腺苷A2b受体的表达,硝酸还原酶法检测血清中NO的含量。结果免疫组化结果,B组的腺苷A2b受体阳性率低于D组( P <0.05),且D组高于A、C两组。硝酸还原酶法结果,B组NO在血清中含量远低于D组( P <0.01),且D组高于A、C两组。结论腺苷可致股动脉狭窄远端腺苷A2b受体表达和NO的浓度明显降低。
基金supported by the National Key R&D Program of China(No.2020YFA0908004)the National Natural Science Foundation of China(Nos.82293684,82293680,82273936,82273929)+1 种基金CAMS Innovation Fund for Medical Science(No.2021-I2M-1-028,2022-I2M-2-002,2022-I2M-1-014,China)Natural Science Fund for Distinguished Young Scholars of Tianjin(No.21JCJQJC00020,China)。
文摘Tolerogenic dendritic cells(tol DCs)facilitate the suppression of autoimmune responses by differentiating regulatory T cells(Treg).The dysfunction of immunotolerance results in the development of autoimmune diseases,such as rheumatoid arthritis(RA).As multipotent progenitor cells,mesenchymal stem cells(MSCs),can regulate dendritic cells(DCs)to restore their immunosuppressive function and prevent disease development.However,the underlying mechanisms of MSCs in regulating DCs still need to be better defined.Simultaneously,the delivery system for MSCs also influences their function.Herein,MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ,maximizing efficacy in vivo.The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines.In the collagen-induced arthritis(CIA)mice model,alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39^(+)CD73^(+)on MSCs.These enzymes hydrolyze ATP to adenosine and activate A_(2A/2B)receptors on immature DCs,further promoting the phenotypic transformation of DCs to tol DCs and regulating naive T cells to Tregs.Therefore,encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression.This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.
文摘Adenosine receptors are a family of G-coupled receptors which mediate the anti-inflammatory and immune-suppressive effects of adenosine in a damaged tissue.A large number of evidence indicate that the accumulation of adenosine under hypoxic conditions favors tumor progression,helping cancer cells to evade immune responses.Tumor cells and/or lymphoid and myeloid cells can express the adenosine-generating enzyme CD73 and/or A2A receptor,which in turn strongly suppresses an effective T-cell-mediated response,while promotes the activity of suppressive cells such as Treg and myeloid-derived suppressor cells.CD73 inhibitors and A2A antagonists,either as single agents,or in combination with immune-checkpoints inhibitors such as anti PD-1 monoclonal antibodies,are currently in Phase I clinical trial in cancer patients.Recent studies show that A2B receptor plays an important role in mediating the pro-tumor effects of adenosine,since its selective blockade can inhibit tumor growth in some murine tumor models.Targeting A2B receptor reduces immunosuppression induced by myeloid cells and inhibits the stromal cells activity within the tumor microenvironment,limiting tumor angiogenesis and metastatic processes.Here,the authors review the current data on involvement of A2B receptor in regulating tumor progression and discuss the development of A2B receptor inhibitors as potential therapeutic agents in cancer treatment.
