Thioredoxin-1 （TRX） is a stress-inducible redox-regulatory protein with antioxidative and anti-inflammatory effects. Here we show that the release of histamine from mast cells elicited by cross-linking of high-affin...Thioredoxin-1 （TRX） is a stress-inducible redox-regulatory protein with antioxidative and anti-inflammatory effects. Here we show that the release of histamine from mast cells elicited by cross-linking of high-affinity receptor for IgE （FcεRI） was significantly suppressed in TRX transgenic （TRX-tg） mice compared to wild type （WT） mice. Intracellular reactive oxygen species （ROS） of mast cells stimulated by IgE and antigen was also reduced in TRX-tg mice compared to WT mice. Whereas there was no difference in the production ofcytokines （IL-6 and TNF-α） from mast cells in response to 2,4-dinitrophenylated bovine serum albumin （DNP-BSA） stimulation in TRX-tg and WT mice. Immunological status of TRX-tg mice inclined to T helper （Th） 2 dominant in primary immune response, although there was no difference in the population of dendritic cells （DCs） and regulatory T cells. We conclude that the histamine release from mast cells in TRX-tg mice is suppressed by inhibition of ROS generation. As ROS are involved in mast cell activation and facilitate mediator release, TRX may be a key signaling molecule regulating the early events in the IgE signaling in mast cells and the allergic inflammation.展开更多
Chronic obstructive pulmonary disease(COPD)is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow.The prevalence of COPD has increased over the last decade and the drugs ...Chronic obstructive pulmonary disease(COPD)is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow.The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it,such as glucocorticoids and bronchodilators,have significant therapeutic effects;however,they also cause side effects,including infection and immunosuppression.Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs.Among these new drugs,we focussed on thioredoxin(Trx).Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance,blocking the NF-κB and MAPK signalling pathways,suppressing the activation and migration of inflammatory cells and the production of cytokines,inhibiting the synthesis and the activation of adhesion factors and growth factors,and controlling the cAMP-PKA and PI3K/Akt signalling pathways.The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses.In addition,Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor(MIF).Taken together,these findings suggest that Trx may be the ideal drug for treating COPD.展开更多
文摘Thioredoxin-1 （TRX） is a stress-inducible redox-regulatory protein with antioxidative and anti-inflammatory effects. Here we show that the release of histamine from mast cells elicited by cross-linking of high-affinity receptor for IgE （FcεRI） was significantly suppressed in TRX transgenic （TRX-tg） mice compared to wild type （WT） mice. Intracellular reactive oxygen species （ROS） of mast cells stimulated by IgE and antigen was also reduced in TRX-tg mice compared to WT mice. Whereas there was no difference in the production ofcytokines （IL-6 and TNF-α） from mast cells in response to 2,4-dinitrophenylated bovine serum albumin （DNP-BSA） stimulation in TRX-tg and WT mice. Immunological status of TRX-tg mice inclined to T helper （Th） 2 dominant in primary immune response, although there was no difference in the population of dendritic cells （DCs） and regulatory T cells. We conclude that the histamine release from mast cells in TRX-tg mice is suppressed by inhibition of ROS generation. As ROS are involved in mast cell activation and facilitate mediator release, TRX may be a key signaling molecule regulating the early events in the IgE signaling in mast cells and the allergic inflammation.
文摘Chronic obstructive pulmonary disease(COPD)is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow.The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it,such as glucocorticoids and bronchodilators,have significant therapeutic effects;however,they also cause side effects,including infection and immunosuppression.Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs.Among these new drugs,we focussed on thioredoxin(Trx).Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance,blocking the NF-κB and MAPK signalling pathways,suppressing the activation and migration of inflammatory cells and the production of cytokines,inhibiting the synthesis and the activation of adhesion factors and growth factors,and controlling the cAMP-PKA and PI3K/Akt signalling pathways.The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses.In addition,Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor(MIF).Taken together,these findings suggest that Trx may be the ideal drug for treating COPD.
