Microbes colonize the gastrointestinal tract are considered as highest complex ecosystem because of having diverse bacterial species and 150 times more genes as compared to the human genome.Imbalance or dysbiosis in g...Microbes colonize the gastrointestinal tract are considered as highest complex ecosystem because of having diverse bacterial species and 150 times more genes as compared to the human genome.Imbalance or dysbiosis in gut bacteria can cause dysregulation in gut homeostasis that subsequently activates the immune system,which leads to the development of inflammatory bowel disease(IBD).Neuromediators,including both neurotransmitters and neuropeptides,may contribute to the development of aberrant immune response.They are emerging as a regulator of inflammatory processes and play a key role in various autoimmune and inflammatory diseases.Neuromediators may influence immune cell’s function via the receptors present on these cells.The cytokines secreted by the immune cells,in turn,regulate the neuronal functions by binding with their receptors present on sensory neurons.This bidirectional communication of the enteric nervous system and the enteric immune system is involved in regulating the magnitude of inflammatory pathways.Alterations in gut bacteria influence the level of neuromediators in the colon,which may affect the gastrointestinal inflammation in a disease condition.Changed neuromediators concentration via dysbiosis in gut microbiota is one of the novel approaches to understand the pathogenesis of IBD.In this article,we reviewed the existing knowledge on the role of neuromediators governing the pathogenesis of IBD,focusing on the reciprocal relationship among the gut microbiota,neuromediators,and host immunity.Understanding the neuromediators and host-microbiota interactions would give a better insight in to the disease pathophysiology and help in developing the new therapeutic approaches for the disease.展开更多
Sepsis is a systemic inflammatory response representing the leading cause of death in critically ill patients,mostly due to multiple organ failure.The gastrointestinal tract plays a pivotal role in the pathogenesis of...Sepsis is a systemic inflammatory response representing the leading cause of death in critically ill patients,mostly due to multiple organ failure.The gastrointestinal tract plays a pivotal role in the pathogenesis of sepsisinduced multiple organ failure through intestinal barrier dysfunction,bacterial translocation and ileus.In this review we address the role of the gastrointestinal tract,the mediators,cell types and transduction pathways involved,based on experimental data obtained from models of inflammation-induced ileus and (preliminary) clinical data.The complex interplay within the gastrointestinal wall between mast cells,residential macrophages and glial cells on the one hand,and neurons and smooth muscle cells on the other hand,involves intracellular signaling pathways,Toll-like receptors and a plethora of neuroactive substances such as nitric oxide,prostaglandins,cytokines,chemokines,growth factors,tryptases and hormones.Multidirectional signaling between the different components in the gastrointestinal wall,the spinal cord and central nervous system impacts inflammation and its consequences.We propose that novel therapeutic strategies should target inflammation on the one hand and gastrointestinal motility,gas-trointestinal sensitivity and even pain signaling on the other hand,for instance by impeding afferent neuronal signaling,by activation of the vagal anti-inflammatory pathway or by the use of pharmacological agents such as ghrelin and ghrelin agonists or drugs interfering with the endocannabinoid system.展开更多
Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorl...Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour expo-sure of interleukin-6 on cortical neurons at various concentrations （0.1, 1, 5 and 10 ng/mL） and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations （2, 4, 8, 24 and 48 hours） by studying voltage-gated Na＋ channels using a patch-clamp technique. Volt-age-clamp recording results demonstrated that interleukin-6 suppressed Na＋ currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na＋channels in rat corti-cal neurons by interleukin-6 is time- and dose-dependent.展开更多
AIM:To characterise expression of interleukin 6(IL-6),a potent proinflammatory cytokine,in the occurrence and development of inflammatory bowel disease(IBD) and investigate its effect on neuroimmunomodulation and immu...AIM:To characterise expression of interleukin 6(IL-6),a potent proinflammatory cytokine,in the occurrence and development of inflammatory bowel disease(IBD) and investigate its effect on neuroimmunomodulation and immune homeostasis regulation.METHODS:In this study,rats with colitis induced by trinitrobenzene sulfonic acid(TNBS) were sacrificed on days 3,7,14,21 and 28 after induction.In the controls,the TNBS was just replaced by equivalent amount of phosphate buffered solution(PBS,0.01 mol/L).IL-6 mRNA expression in brain and colon tissues in each phase was evaluated by real-time reverse transcriptionpolymerase chain reaction,and cellular localisation and protein level of IL-6 was determined by immunohistochemistry.RESULTS:At day 7,mRNA expression of IL-6 was significantly higher in the colon and brain of IBD rats than that of the controls.The protein level was also significantly higher in colon,hypothalamus and cerebral cortex of IBD rats compared with the controls.So there are similar temporal trends in IL-6 mRNA expression and protein levels in all positions with a persistent increase to a peak at day 7,followed by a decline and gradual return to normal levels.CONCLUSION:These results revealed that changes in IL-6 expression in brain and colon tissues occur in different phases of IBD.Therefore,we propose that the nerve centre regulates and controls the occurrence and development of IBD via IL-6.展开更多
Objective To investigate T cell activation following facial nerve axotomization and latent neuroimmunologic mechanisms in traumatic facial paralysis.Methods A murine model of facial nerve transaction was used.Lymphocy...Objective To investigate T cell activation following facial nerve axotomization and latent neuroimmunologic mechanisms in traumatic facial paralysis.Methods A murine model of facial nerve transaction was used.Lymphocytes from cervical and mesenteric lymph nodes in BABL/c mice at specific times were collected and expression rates of CD69 on T cells were assessed by flow cytometry.Results Infiltrating T cells were detected around the facial neurons in the facial nerve nucleus in mice whose facial nerve was transected.Immunofluorescent staining showed recruitment of activated T cells.Three days post-facial nerve transection,the expression rate of CD69 on T cells from cervical draining lymphoid nodes(CDLNs) was significantly different from that on T cells from mesenteric lymph nodes(MLNs)(P =0.0457),whereas the latter was similar to that in animals undergoing sham surgeries and that in blank control animals(p= 0.2817 and 0.2724,respectively).Two weeks post-nerve transection,the T cell CD69 expression rate from CDLNs remained at a higher level and than that in the sham-operation animals(p= 0.0007).At two weeks,CD69 expression rate on T cells from MLNs was also up-regulated and different compared with the sham-operation animals and with itself at three days post-operation(p= 0.0082 and 0.0133,respectively).Conclusion T cells appear to be activated and up-regulated in CDLNs following facial nerve transection.There is even evidence of T cell activation in MLNs at 2 weeks post-nerve transection.This suggestes an alteration of immune response from local to general immunity in the acute stage of facial nerve trauma,which may help coordinating and controlling the scales and orientation of the neuroimmune response during the pathogenesis and progression of facial nerve trauma.展开更多
Experimental research has recently shown that acupuncture induces the formation of opioid-like peptides (OLPs) in animals. In order to provide further evidence, we tested the beta-endorphin levels and other parameters...Experimental research has recently shown that acupuncture induces the formation of opioid-like peptides (OLPs) in animals. In order to provide further evidence, we tested the beta-endorphin levels and other parameters (VIP, lymphocyte subsets, NK cells and monocyte phagocytosis) in a group of 90 patients suffering from various painful disorders treated with acupuncture. Zusanli (St 36) and Hegu (LI 4) acupoints were selected. A homogeneous group of 30 subjects was used as control. Evaluation of the above parameters was made with 3 series of blood tests before treatment, 30 minutes and 24 hours after acupuncture treatment. In the acupuncture group, the following results were achieved: 1) A considerable increase in beta-endorphin levels remained high even 24 hours after acupuncture treatment. In addition, we demonstrated an inverted correlation between beta-endorphins and VIP; 2) 30 minutes after acupuncture session, 80% of the treated patients showed a significant increase of CD3 and CD4 values and an increase of CD8 24 hours after stimulation; 3) Monocyte phagocytosis was increased in 45% of the treated subjects 30 minutes from starting treatment, and in 100% of them after 24 hours. The percentage of NK cells was also increased in 40% of cases after 30 minutes, and in 50% after 24 hours. However, in the control group, no such significant changes in immune parameters were found.展开更多
Objective： To investigate the clinical efficacy and immunological mechanism of herbal cake-partitioned moxibustion for aging process. Method： The herbal cake-partitioned moxibustion was adopted for 223 cases to obse...Objective： To investigate the clinical efficacy and immunological mechanism of herbal cake-partitioned moxibustion for aging process. Method： The herbal cake-partitioned moxibustion was adopted for 223 cases to observe the aging scores before and after the treatment. Apart from that, the T-lymphocyte subsets and changes of IL-2 and β-EP were also detected. Results： After treatment, the aging scores of 223 cases were all substantially reduced, along with an improvement of clinical symptoms, a strengthened cellular immune function, and an increase of total T-lymphocyte count. In addition, the CD4＋/CD8＋ ratio was restored normal, the synthesis or secretion of IL-2 was increased and the β-EP （as the neurotransmitter to modulate immune function） was substantially improved. Conclusion： The aging process is closely associated with the immune function. Moxibustion can modulate abnormal immune function and stabilize homeostasis and thus delay the aging process.展开更多
Background The immunomodulatory effects of glucocorticoids （GCs） have been described as bimodal. High concentration of GCs exerts immunosuppressive effects and low levels of GCs are immunopermissive. While the immun...Background The immunomodulatory effects of glucocorticoids （GCs） have been described as bimodal. High concentration of GCs exerts immunosuppressive effects and low levels of GCs are immunopermissive. While the immunosuppressive mechanisms of GCs have been investigated intensely, the immunopermissive effects of GCs remain unclear. A lot of studies showed GCs could exert rapid non-genomic actions. We herein studied the rapid immunopromoting effects of GCs.Methods We observed the rapid （within 30 minutes） effects of corticosterone on respiratory burst of mouse peritoneal macrophages and studied their mechanisms. The superoxide anions were measured by cytochrome C reduction assay.Protein kinase C phosphorylation was measured by Western blotting and membrane fluidity was evaluated by fluorescence polarization measurement.Results The 10-8 mol/L and 10-7 mol/L corticosterone rapidly increased the superoxide anions production by macrophages, which were insensitive to GC-receptor antagonist, mifepristone, and protein-synthesis inhibitor,cycloheximide. Corticosterone coupled to bovine serum albumin was able to mimic the effects of corticosterone. The effects were independent of protein kinase C pathway and the change in membrane fluidity.Conclusions The results indicate that corticosterone rapidly promote the superoxide anions production by mouse peritoneal macrophages may through non-genomic mechanisms. This study may contribute to understanding the effects of GCs under stress condition and the physiological significance of nongenomic effects of GCs.展开更多
Acupuncture can modulate immune responses and thus produce good therapeutical results when used as an subsidiary measure to treat some infectious diseases, tumors and unbalanced immune functions. ZHAO et al. held that...Acupuncture can modulate immune responses and thus produce good therapeutical results when used as an subsidiary measure to treat some infectious diseases, tumors and unbalanced immune functions. ZHAO et al. held that endogenous opiates participate in the modulation of immune responses by acupuncture. It has been reported abroad展开更多
Chronic respiratory diseases(CRDs)are among the most common noncommunicable diseases globally,with high morbidity and mortality rates.Acupuncture,a treatment method derived from Traditional Chinese Medicine,has been s...Chronic respiratory diseases(CRDs)are among the most common noncommunicable diseases globally,with high morbidity and mortality rates.Acupuncture,a treatment method derived from Traditional Chinese Medicine,has been shown to be effective at treating CRDs,with little risk of adverse effects.Scientific research on the mechanisms underlying the effects of acupuncture,especially,its immune regulatory function,has rapidly advanced in recent years.Herein,the diverse immune regulatory mechanisms underlying the beneficial effects of acupuncture are summarized from the perspectives of innate immunity,adaptive immunity,and neuroimmunity.A better understanding of these mechanisms will ultimately provide a scientific basis for the clinical use of acupuncture for the treatment of CRDs.展开更多
文摘Microbes colonize the gastrointestinal tract are considered as highest complex ecosystem because of having diverse bacterial species and 150 times more genes as compared to the human genome.Imbalance or dysbiosis in gut bacteria can cause dysregulation in gut homeostasis that subsequently activates the immune system,which leads to the development of inflammatory bowel disease(IBD).Neuromediators,including both neurotransmitters and neuropeptides,may contribute to the development of aberrant immune response.They are emerging as a regulator of inflammatory processes and play a key role in various autoimmune and inflammatory diseases.Neuromediators may influence immune cell’s function via the receptors present on these cells.The cytokines secreted by the immune cells,in turn,regulate the neuronal functions by binding with their receptors present on sensory neurons.This bidirectional communication of the enteric nervous system and the enteric immune system is involved in regulating the magnitude of inflammatory pathways.Alterations in gut bacteria influence the level of neuromediators in the colon,which may affect the gastrointestinal inflammation in a disease condition.Changed neuromediators concentration via dysbiosis in gut microbiota is one of the novel approaches to understand the pathogenesis of IBD.In this article,we reviewed the existing knowledge on the role of neuromediators governing the pathogenesis of IBD,focusing on the reciprocal relationship among the gut microbiota,neuromediators,and host immunity.Understanding the neuromediators and host-microbiota interactions would give a better insight in to the disease pathophysiology and help in developing the new therapeutic approaches for the disease.
文摘Sepsis is a systemic inflammatory response representing the leading cause of death in critically ill patients,mostly due to multiple organ failure.The gastrointestinal tract plays a pivotal role in the pathogenesis of sepsisinduced multiple organ failure through intestinal barrier dysfunction,bacterial translocation and ileus.In this review we address the role of the gastrointestinal tract,the mediators,cell types and transduction pathways involved,based on experimental data obtained from models of inflammation-induced ileus and (preliminary) clinical data.The complex interplay within the gastrointestinal wall between mast cells,residential macrophages and glial cells on the one hand,and neurons and smooth muscle cells on the other hand,involves intracellular signaling pathways,Toll-like receptors and a plethora of neuroactive substances such as nitric oxide,prostaglandins,cytokines,chemokines,growth factors,tryptases and hormones.Multidirectional signaling between the different components in the gastrointestinal wall,the spinal cord and central nervous system impacts inflammation and its consequences.We propose that novel therapeutic strategies should target inflammation on the one hand and gastrointestinal motility,gas-trointestinal sensitivity and even pain signaling on the other hand,for instance by impeding afferent neuronal signaling,by activation of the vagal anti-inflammatory pathway or by the use of pharmacological agents such as ghrelin and ghrelin agonists or drugs interfering with the endocannabinoid system.
基金supported by a grant from the National Natural Science Foundation of China,No.30972766,31170852,81001322,81172795,81173048the Specialized Research Fund for the Doctoral Program of Colleges and Universities,No.20094402110004
文摘Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour expo-sure of interleukin-6 on cortical neurons at various concentrations （0.1, 1, 5 and 10 ng/mL） and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations （2, 4, 8, 24 and 48 hours） by studying voltage-gated Na＋ channels using a patch-clamp technique. Volt-age-clamp recording results demonstrated that interleukin-6 suppressed Na＋ currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na＋channels in rat corti-cal neurons by interleukin-6 is time- and dose-dependent.
基金Supported by The grant from the National Natural Science Foundation of China,No 30871840No 30901057
文摘AIM:To characterise expression of interleukin 6(IL-6),a potent proinflammatory cytokine,in the occurrence and development of inflammatory bowel disease(IBD) and investigate its effect on neuroimmunomodulation and immune homeostasis regulation.METHODS:In this study,rats with colitis induced by trinitrobenzene sulfonic acid(TNBS) were sacrificed on days 3,7,14,21 and 28 after induction.In the controls,the TNBS was just replaced by equivalent amount of phosphate buffered solution(PBS,0.01 mol/L).IL-6 mRNA expression in brain and colon tissues in each phase was evaluated by real-time reverse transcriptionpolymerase chain reaction,and cellular localisation and protein level of IL-6 was determined by immunohistochemistry.RESULTS:At day 7,mRNA expression of IL-6 was significantly higher in the colon and brain of IBD rats than that of the controls.The protein level was also significantly higher in colon,hypothalamus and cerebral cortex of IBD rats compared with the controls.So there are similar temporal trends in IL-6 mRNA expression and protein levels in all positions with a persistent increase to a peak at day 7,followed by a decline and gradual return to normal levels.CONCLUSION:These results revealed that changes in IL-6 expression in brain and colon tissues occur in different phases of IBD.Therefore,we propose that the nerve centre regulates and controls the occurrence and development of IBD via IL-6.
基金supported by grants from the National "Tenth-Five" Scientific & Technological Problem-Tackling Project(№:2004BA720A18-01)Social Welfare Foundation of Scientific Research Institutes of Chinese Ministry of Science & Technology(№:2002DB40097)
文摘Objective To investigate T cell activation following facial nerve axotomization and latent neuroimmunologic mechanisms in traumatic facial paralysis.Methods A murine model of facial nerve transaction was used.Lymphocytes from cervical and mesenteric lymph nodes in BABL/c mice at specific times were collected and expression rates of CD69 on T cells were assessed by flow cytometry.Results Infiltrating T cells were detected around the facial neurons in the facial nerve nucleus in mice whose facial nerve was transected.Immunofluorescent staining showed recruitment of activated T cells.Three days post-facial nerve transection,the expression rate of CD69 on T cells from cervical draining lymphoid nodes(CDLNs) was significantly different from that on T cells from mesenteric lymph nodes(MLNs)(P =0.0457),whereas the latter was similar to that in animals undergoing sham surgeries and that in blank control animals(p= 0.2817 and 0.2724,respectively).Two weeks post-nerve transection,the T cell CD69 expression rate from CDLNs remained at a higher level and than that in the sham-operation animals(p= 0.0007).At two weeks,CD69 expression rate on T cells from MLNs was also up-regulated and different compared with the sham-operation animals and with itself at three days post-operation(p= 0.0082 and 0.0133,respectively).Conclusion T cells appear to be activated and up-regulated in CDLNs following facial nerve transection.There is even evidence of T cell activation in MLNs at 2 weeks post-nerve transection.This suggestes an alteration of immune response from local to general immunity in the acute stage of facial nerve trauma,which may help coordinating and controlling the scales and orientation of the neuroimmune response during the pathogenesis and progression of facial nerve trauma.
文摘Experimental research has recently shown that acupuncture induces the formation of opioid-like peptides (OLPs) in animals. In order to provide further evidence, we tested the beta-endorphin levels and other parameters (VIP, lymphocyte subsets, NK cells and monocyte phagocytosis) in a group of 90 patients suffering from various painful disorders treated with acupuncture. Zusanli (St 36) and Hegu (LI 4) acupoints were selected. A homogeneous group of 30 subjects was used as control. Evaluation of the above parameters was made with 3 series of blood tests before treatment, 30 minutes and 24 hours after acupuncture treatment. In the acupuncture group, the following results were achieved: 1) A considerable increase in beta-endorphin levels remained high even 24 hours after acupuncture treatment. In addition, we demonstrated an inverted correlation between beta-endorphins and VIP; 2) 30 minutes after acupuncture session, 80% of the treated patients showed a significant increase of CD3 and CD4 values and an increase of CD8 24 hours after stimulation; 3) Monocyte phagocytosis was increased in 45% of the treated subjects 30 minutes from starting treatment, and in 100% of them after 24 hours. The percentage of NK cells was also increased in 40% of cases after 30 minutes, and in 50% after 24 hours. However, in the control group, no such significant changes in immune parameters were found.
文摘Objective： To investigate the clinical efficacy and immunological mechanism of herbal cake-partitioned moxibustion for aging process. Method： The herbal cake-partitioned moxibustion was adopted for 223 cases to observe the aging scores before and after the treatment. Apart from that, the T-lymphocyte subsets and changes of IL-2 and β-EP were also detected. Results： After treatment, the aging scores of 223 cases were all substantially reduced, along with an improvement of clinical symptoms, a strengthened cellular immune function, and an increase of total T-lymphocyte count. In addition, the CD4＋/CD8＋ ratio was restored normal, the synthesis or secretion of IL-2 was increased and the β-EP （as the neurotransmitter to modulate immune function） was substantially improved. Conclusion： The aging process is closely associated with the immune function. Moxibustion can modulate abnormal immune function and stabilize homeostasis and thus delay the aging process.
基金This work was supported by grants from the Military Twelfth Five-Year Plan and National Natural Science Foundation of China （No. 30873077, No. 30971083） The authors declared no conflicts of interests.
文摘Background The immunomodulatory effects of glucocorticoids （GCs） have been described as bimodal. High concentration of GCs exerts immunosuppressive effects and low levels of GCs are immunopermissive. While the immunosuppressive mechanisms of GCs have been investigated intensely, the immunopermissive effects of GCs remain unclear. A lot of studies showed GCs could exert rapid non-genomic actions. We herein studied the rapid immunopromoting effects of GCs.Methods We observed the rapid （within 30 minutes） effects of corticosterone on respiratory burst of mouse peritoneal macrophages and studied their mechanisms. The superoxide anions were measured by cytochrome C reduction assay.Protein kinase C phosphorylation was measured by Western blotting and membrane fluidity was evaluated by fluorescence polarization measurement.Results The 10-8 mol/L and 10-7 mol/L corticosterone rapidly increased the superoxide anions production by macrophages, which were insensitive to GC-receptor antagonist, mifepristone, and protein-synthesis inhibitor,cycloheximide. Corticosterone coupled to bovine serum albumin was able to mimic the effects of corticosterone. The effects were independent of protein kinase C pathway and the change in membrane fluidity.Conclusions The results indicate that corticosterone rapidly promote the superoxide anions production by mouse peritoneal macrophages may through non-genomic mechanisms. This study may contribute to understanding the effects of GCs under stress condition and the physiological significance of nongenomic effects of GCs.
文摘Acupuncture can modulate immune responses and thus produce good therapeutical results when used as an subsidiary measure to treat some infectious diseases, tumors and unbalanced immune functions. ZHAO et al. held that endogenous opiates participate in the modulation of immune responses by acupuncture. It has been reported abroad
基金Supported by the Sichuan Science and Technology Application Foundation Plan(No.2021YFS0039)the Project of Sichuan Provincial Administration of Traditional Chinese Medicine(No.2020LC0031)the foundation of Chengdu University of Traditional Chinese Medicine(No.YYZX2019039 and YYZX2019038)。
文摘Chronic respiratory diseases(CRDs)are among the most common noncommunicable diseases globally,with high morbidity and mortality rates.Acupuncture,a treatment method derived from Traditional Chinese Medicine,has been shown to be effective at treating CRDs,with little risk of adverse effects.Scientific research on the mechanisms underlying the effects of acupuncture,especially,its immune regulatory function,has rapidly advanced in recent years.Herein,the diverse immune regulatory mechanisms underlying the beneficial effects of acupuncture are summarized from the perspectives of innate immunity,adaptive immunity,and neuroimmunity.A better understanding of these mechanisms will ultimately provide a scientific basis for the clinical use of acupuncture for the treatment of CRDs.
