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Purpose@#Wnt pathway is closely related to neurodevelopmental process associated with cognitive function. After administration of valproic acid to the pregnant mice, the effect of swimming exercise of pregnant mice on the memory, neuronal production, and apoptosis of pups was studied in relation with Wnt/β-catenin signaling pathway. @*Methods@#On day 12 of pregnancy, mice were injected subcutaneously with 400-mg/kg valproic acid. The pregnant mice in the control with swimming exercise group and in the valproic acid injection with swimming exercise group were allowed for swimming for 30 minutes one time per a day, repeated 5 days per a week, during 3 weeks. Step-through avoidance task and Morris water maze task for memory function, immunohistochemistry for 5-bromo-2’-deoxyuridine (BrdU)-positive cells and western blot for brain-derived neurotrophic factor (BDNF), Wnt, β-catenin, Bcl-2 related X protein (Bax), B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 were carried out. @*Results@#Maternal swimming exercise during pregnancy improved memory function, increased BDNF expression, and neuronal proliferation in the valproic acid injected pups. Maternal swimming exercise during pregnancy suppressed Wnt expression and phosphorylation of β-catenin in the valproic acid injected pups. Maternal swimming exercise inhibited Bax and cleaved caspase-3 expression and increased Bcl-2 expression in the valproic acid injected pups. @*Conclusions@#Maternal swimming exercise during pregnancy improved memory function by increasing cell proliferation and inhibiting apoptosis through Wnt/β-catenin signaling cascade activation in the valproic acid injected pups. Maternal swimming exercise during pregnancy may have a protective effect on factors that induce autism in the fetus.
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Purpose@#Poloxamer-407 (P-407) is used to induce hyperlipidemia. Exercise is effective in improving arteriosclerosis and cognitive impairment. In this research, the effect of treadmill running on short-term memory in the P-407-treated hyperlipidemia rats was studied focusing on neuroinflammation. @*Methods@#Rats were classified in normal group, normal and treadmill exercise group, P-407-treated group, and P-407-treated and treadmill exercise group. Hyperlipidemia rats were made by single intraperitoneal injection with P-407 (500 mg/kg). Treadmill exercise was conducted for 30 minutes once a day, 5 days per week during 28 days. Step-down avoidance task was done to measure short-term memory. Glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 were assessed by immunohistochemistry. Expression of adhesion molecules and proinflammatory cytokines was determined by western blot analysis. @*Results@#Treadmill exercise alleviated lipid profiles in the P-407-induced hyperlipidemia rats. Treadmill exercise improved short-term memory, inhibited reactive astrogliosis and microglia activation, and suppressed expression of adhesion molecules and proinflammatory cytokines in the hyperlipidemic rats. @*Conclusions@#Treadmill exercise exerts alleviating effect on memory deficits by inhibiting hippocampal neuroinflammation in the hyperlipidemia. The current results suggest that treadmill running serves as the treatment strategy for the cognitive dysfunction caused by hyperlipidemia.
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Background@#Bovine tuberculosis (TB) is caused by Mycobacterium bovis, a well-known cause of zoonotic tuberculosis in cattle and deer, and has been investigated in many physiological and molecular studies. However, detailed genome-level studies of M. bovis have not been performed in Korea. @*Objectives@#To survey whole genome-wide single-nucleotide polymorphism (SNP) variants in Korean M. bovis field isolates and to define M. bovis groups in Korea by comparing SNP typing with spoligotyping and variable number tandem repeat typing. @*Methods@#A total of 46 M. bovis field isolates, isolated from laryngopharyngeal lymph nodes and lungs of Korean cattle, wild boar, and Korean water deer, were used to identify SNPs by performing whole-genome sequencing. SNP sites were confirmed via polymerase chain reaction using 87 primer pairs. @*Results@#We identified 34 SNP sites with different frequencies across M. bovis isolates, and performed SNP typing and epidemiological analysis, which divided the 46 field isolates into 16 subtypes. @*Conclusions@#Through SNP analysis, detailed differences in samples with identical spoligotypes could be detected. SNP analysis is, therefore, a useful epidemiological tracing tool that could enable better management of bovine TB, thus preventing further outbreaks and reducing the impact of this disease.
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Background@#Bovine tuberculosis (TB) is caused by Mycobacterium bovis, a well-known cause of zoonotic tuberculosis in cattle and deer, and has been investigated in many physiological and molecular studies. However, detailed genome-level studies of M. bovis have not been performed in Korea. @*Objectives@#To survey whole genome-wide single-nucleotide polymorphism (SNP) variants in Korean M. bovis field isolates and to define M. bovis groups in Korea by comparing SNP typing with spoligotyping and variable number tandem repeat typing. @*Methods@#A total of 46 M. bovis field isolates, isolated from laryngopharyngeal lymph nodes and lungs of Korean cattle, wild boar, and Korean water deer, were used to identify SNPs by performing whole-genome sequencing. SNP sites were confirmed via polymerase chain reaction using 87 primer pairs. @*Results@#We identified 34 SNP sites with different frequencies across M. bovis isolates, and performed SNP typing and epidemiological analysis, which divided the 46 field isolates into 16 subtypes. @*Conclusions@#Through SNP analysis, detailed differences in samples with identical spoligotypes could be detected. SNP analysis is, therefore, a useful epidemiological tracing tool that could enable better management of bovine TB, thus preventing further outbreaks and reducing the impact of this disease.
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Purpose@#Thrombotic stroke is a type of ischemic stroke characterized by motor dysfunction and memory impairments. In the present study, the effect of treadmill exercise on motor function and short-term memory was evaluated in relation with synaptic plasticity in the mice with photothrombotic stroke. @*Methods@#Photothrombotic stroke was induced by cortical photothrombotic vascular occlusion. The mice in the treadmill exercise groups performed running on a motorized treadmill for 28 days. Motor function was determined using rota-rod test and foot fault test. Step-through avoidance task was conducted to evaluate short-term memory. Immunohistochemistry for 5-bromo-2′-deoxyuridine and doublecortin was conducted to detect new cell generation. Postsynaptic density protein 95, synaptophysin, brain-derived neurotrophic factor (BDNF), and tyrosine kinase B receptor (TrkB) were determined using western blot. The number of dendritic spines was determined using Golgi stain. @*Results@#Treadmill exercise improved motor function and short-term memory in mice with the photothrombotic stroke. The infarct size was reduced and the number of dendritic spines and expression of postsynaptic density protein 95 and synaptophysin in the peri-infarct cortex and hippocampus were increased by treadmill exercise in photothrombotic stroke mice. Treadmill exercise enhanced neurogenesis through increasing the expression of the hippocampal BDNF and TrkB in photothrombotic stroke mice. @*Conclusions@#Treadmill exercise improved motor function and short-term memory through increasing synaptic plasticity and neurogenesis in photothrombotic stroke mice. Treadmill exercise can be used as an effective treatment strategy to improve brain function related to stroke.
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PURPOSE@#Hyperlipidemia, which promotes the development of atherosclerosis, ischemic stroke, and other forms of brain injury, can be induced by poloxamer-407. Berberine is a primary pharmacological active component of Coptidis Rhizoma that has a number of therapeutic activities. This study investigated the effects of berberine on poloxamer-407-induced brain inflammation by evaluating its effects on short-term memory, cell proliferation, inflammation, and apoptosis in the hippocampus.@*METHODS@#To induce hyperlipidemia in a rat model, 500 mg/kg of poloxamer-407 was injected intraperitoneally. Berberine was orally administered to the rats in the berberine-treated groups once a day for 4 weeks. The step-down task avoidance task was performed to measure short-term memory. An analysis of serum lipids, immunohistochemistry for 5-bromo-2′-deoxyuridine, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba1) in the dentate gyrus, and western blot analysis for Bax, Bcl-2, and cytochrome c in the hippocampus were performed.@*RESULTS@#In hyperlipidemic rats, berberine reduced the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol and increased the level of high-density lipoprotein cholesterol in hyperlipidemic rats. Berberine also increased cell proliferation and short-term memory, as well as decreasing the expression of GFAP, Iba1, Bax, and cytochrome c and increasing Bcl-2 expression.@*CONCLUSIONS@#Berberine treatment improved short-term memory in hyperlipidemia by increasing neuronal proliferation and inhibiting neuronal apoptosis. Berberine treatment also improved lipid metabolism.
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PURPOSE@#Chemotherapy is associated with the side effects including damage to the mitochondrial DNA. Doxorubicin (DOX) serves as a chemotherapeutic agent for the patients with breast cancer or prostate cancer. DOX causes muscle weakness and fatigue. We investigated the effects of treadmill exercise on DOX-induced apoptosis and mitochondrial dysfunction in relation to central fatigue. For this study, we used the rat model of DOX-induced muscle damage.@*METHODS@#DOX (2 mg/kg) was intraperitoneally injected 1 time per week for 4 weeks. Treadmill running continued 5 days per week for 4 weeks. Muscle strength and fatigue index in the gastrocnemius were measured. Immunohistochemistry for the expressions of tryptophan hydroxylase (TPH) and 5-hydroxytryptamine (5-HT) in the dorsal raphe was conducted. We used western blot analysis for the expressions of Bax, Bcl-2, and caspases-3 in the gastrocnemius. Mitochondrial function in the gastrocnemius was also evaluated.@*RESULTS@#DOX treatment decreased muscle strength with increase of fatigue index in the gastrocnemius. Mitochondria function was deteriorated and apoptosis in the gastrocnemius was enhanced by DOX treatment. Expressions of TPH and 5-HT in the dorsal raphe were increased by DOX treatment. Treadmill exercise attenuated DOX-induced muscle fatigue and impairment of mitochondria function. Apoptosis in the gastrocnemius was inhibited and over-expression of TPH and 5-HT was suppressed by treadmill exercise.@*CONCLUSIONS@#Apoptosis was enhanced and mitochondria function was deteriorated by DOX treatment, resulting in muscle weakness and central fatigue. Treadmill exercise suppressed apoptosis and prevented deterioration of mitochondria function in muscle, resulting in alleviation of muscle weakness and central fatigue during DOX therapy.
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PURPOSE: Rotenone is the most widely used neurotoxin for the making Parkinson disease (PD) animal model. The neurodegenerative disorder PD shows symptoms, such as slowness of movements, tremor at resting, rigidity, disturbance of gait, and instability of posture. We investigated whether treadmill running improves motor ability using rotenone-caused PD rats. The effect of treadmill running on PD was also assessed in relation with apoptosis of cerebellar Purkinje cells. METHODS: Treadmill running was applied to the rats in the exercise groups for 30 minutes once a day for 4 weeks, starting 4 weeks after birth. We used rota-rod test for the determination of motor coordination and balance. In this experiment, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, immunohistochemistry for calbindin, glial fibrillary acidic protein (GFAP), Iba-1, and western blot analysis for Bax and Bcl-2 were performed. RESULTS: Treadmill running enhanced motor balance and coordination by preventing the loss of Purkinje cells in the cerebellar vermis. Treadmill running suppressed PD-induced expression of GFAP-positive reactive astrocytes and Iba-1-positive microglia, showing that treadmill running suppressed reactive astrogliosis and microglia activation. Treadmill running suppressed TUNEL-positive cell number and Bax expression and enhanced Bcl-2 expression, demonstrating that treadmill running inhibited the progress of apoptosis in the cerebellum of rotenone-induced PD rats. CONCLUSIONS: Treadmill running improved motor ability of the rotenone-induced PD rats by inhibiting apoptosis in the cerebellum. Apoptosis suppressing effect of treadmill running on rotenone-induced PD was achieved via suppression of reactive astrocyte and inhibition of microglial activation.
Subject(s)
Animals , Rats , Apoptosis , Astrocytes , Blotting, Western , Calbindins , Cell Count , Cerebellar Vermis , Cerebellum , Gait , Glial Fibrillary Acidic Protein , Immunohistochemistry , Microglia , Models, Animal , Neurodegenerative Diseases , Parkinson Disease , Parturition , Posture , Purkinje Cells , Rotenone , Running , TremorABSTRACT
PURPOSE: Traumatic brain injury (TBI) causes cognitive impairments, motor deficits, and neuropsychiatric/behavioral deficits problems. Transplantation of bone marrow stromal cells (BMSCs) facilitates functional recovery from brain insults. Treadmill exercise increases neurogenesis and inhibits apoptosis. In this study, we investigated the effects of BMSC transplantation in combination with treadmill exercise on memory function, by evaluating its effect on neurogenesis and apoptosis in the hippocampus following TBI. METHODS: TBI was induced using an electromagnetic-controlled cortical impact device. BMSCs were transplanted into both sides of traumatic scar region 1 week after TBI induction. One week after transplantation of BMSCs, the rats in the exercise groups were trained to run on a treadmill for 30 minutes once daily for 28 days. Step-down avoidance task and radial 8-arm maze test were conducted. Levels of 5-bromo-2'-deoxyuridine and caspase-3 were evaluated using immunohistochemistry. Western blot was used to evaluate the expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), total-extracellular signal-regulated kinase 1 and 2 (t-ERK1/2), phosphorylated-ERK1/2 (p-ERK1/2), Bcl-2, and Bax. RESULTS: TBI deteriorated memory function, suppressed neurogenesis, and accelerated apoptosis in the hippocampus. Treadmill exercise and BMSC transplantation independently improved memory function by increasing neurogenesis with suppression of apoptosis through the BDNF-ERK pathway in the TBI-induced rats. Combination of BMSC transplantation with treadmill exercise showed additional enhancement of neurogenesis and suppression of apoptosis in the hippocampus. CONCLUSIONS: The present study shows that treadmill exercise may aid the therapeutic effect of BMSC transplantation on TBI in rats.
Subject(s)
Animals , Rats , Apoptosis , Blotting, Western , Bone Marrow , Brain , Brain Injuries , Brain-Derived Neurotrophic Factor , Caspase 3 , Cicatrix , Cognition Disorders , Exercise Test , Hippocampus , Immunohistochemistry , Memory , Mesenchymal Stem Cells , Neurogenesis , Neuroprotective Agents , Phosphotransferases , Protein-Tyrosine KinasesABSTRACT
PURPOSE: Stress during pregnancy is a risk factor for the development of anxiety-related disorders in offspring later in life. The effects of treadmill exercise on anxiety-like behaviors and hippocampal cell proliferation were investigated using rats exposed to prenatal stress. METHODS: Exposure of pregnant rats to a hunting dog in an enclosed room was used to induce stress. Anxiety-like behaviors of offspring were evaluated using the elevated plus maze test. Immunohistochemistry for the detection of 5-bromo-2'-deoxyuridine and doublecortin (DCX) in the hippocampal dentate gyrus and 5-hydroxytryptamine 1A receptors (5-HT(1A)) in the dorsal raphe was conducted. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) levels in the hippocampus were evaluated by western blot analysis. RESULTS: Offspring of maternal rats exposed to stress during pregnancy showed anxiety-like behaviors. Offspring also showed reduced expression of BDNF, TrkB, and DCX in the dentate gyrus, decreased cell proliferation in the hippocampus, and reduced 5-HT(1A) expression in the dorsal raphe. Postnatal treadmill exercise by offspring, but not maternal exercise during pregnancy, enhanced cell proliferation and expression of these proteins. CONCLUSIONS: Postnatal treadmill exercise ameliorated anxiety-like behaviors in offspring of stressed pregnant rats, and the alleviating effect of exercise on these behaviors is hypothesized to result from enhancement of cell proliferation through 5-HT(1A) activation in offspring rats.
Subject(s)
Animals , Dogs , Pregnancy , Rats , Anxiety , Blotting, Western , Brain-Derived Neurotrophic Factor , Bromodeoxyuridine , Cell Proliferation , Dentate Gyrus , Dorsal Raphe Nucleus , Exercise Test , Hippocampus , Immunohistochemistry , Prenatal Exposure Delayed Effects , Protein-Tyrosine Kinases , Receptor, Serotonin, 5-HT1A , Risk Factors , SerotoninABSTRACT
PURPOSE: Stress is associated with depression, which induces many psychiatric disorders. Serotonin, also known as 5-hydroxy-tryptamine (5-HT), acts as a biochemical messenger and regulator in the brain. It also mediates several important physiological functions. Depression is closely associated with an overactive bladder. In the present study, we investigated the effect of treadmill exercise on stress-induced depression while focusing on the expression of 5-HT 1A (5-H(1A)) receptors in the dorsal raphe. METHODS: Stress was induced by applying a 0.2-mA electric foot shock to rats. Each set of electric foot shocks comprised a 6-second shock duration that was repeated 10 times with a 30-second interval. Three sets of electric foot shocks were applied each day for 7 days. For the confirmation of depressive state, a forced swimming test was performed. To visualize the expression of 5-HT and tryptophan hydroxylase (TPH), immunohistochemistry for 5-HT and TPH in the dorsal raphe was performed. Expression of 5-H(1A) receptors was determined by western blot analysis. RESULTS: A depressive state was induced by stress, and treadmill exercise alleviated the depression symptoms in the stress-induced rats. Expressions of 5-HT, TPH, and HT 1A in the dorsal raphe were reduced by the induction of stress. Treadmill exercise increased 5-HT, TPH, and HT 1A expressions in the stress-induced rats. CONCLUSIONS: Treadmill exercise enhanced 5-HT synthesis through the up-regulation of 5-HT(1A) receptors, and improved the stress-induced depression. In the present study, treadmill exercise improved depression symptoms by enhancing 5-HT(1A) receptor expression. The present results suggest that treadmill exercise might be helpful for the alleviation of overactive bladder and improve sexual function.
Subject(s)
Animals , Rats , Blotting, Western , Brain , Depression , Exercise Test , Exercise , Foot , Immunohistochemistry , Physical Exertion , Receptor, Serotonin, 5-HT1A , Serotonin , Shock , Stress, Psychological , Tryptophan Hydroxylase , Up-Regulation , Urinary Bladder, OveractiveABSTRACT
PURPOSE: Neurogenic lower urinary tract dysfunction (NLUTD) is a possible consequence of several neurological disorders. NLUTD may produce debilitating symptoms and serious complications, such as chronic renal failure, and recurrent urinary tract infections. Many animal studies of NLUTD symptoms have focused on animal models of cerebral ischemia. In the present study, we investigated the effects of treadmill exercise on memory function and its relation to cell proliferation and apoptosis in the hippocampus, following transient global ischemia in gerbils. METHODS: To induce transient global ischemia in gerbil, both common carotid arteries were occluded for 5 minutes. Gerbils in the exercise groups were forced to run on a treadmill exercise for 30 minutes once a day for 2 weeks. Step-down avoidance task and Y maze task were performed. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-staining, immunohistochemistry for 5-bromo-2'-deoxyridine, doublecortin, caspase-3, and Western blot for brain-derived neurotrophic factor (BDNF), Bax, Bcl-2, cytochrome c, caspase-3 were conducted. RESULTS: Ischemia caused memory impairment with an increase of cell proliferation, BDNF expression, and apoptosis in the hippocampus. Treadmill exercise improved memory function with further increase of cell proliferation and BDNF expression and a decrease of apoptosis. CONCLUSIONS: The animal model that we have developed and our assessment of the relation between exercise and brain function can be useful tools for future investigations of NLUTD symptoms associated with stroke, particularly ischemic stroke. The present study suggests that treadmill exercise promoted the recovery of brain function after cerebral ischemia.
Subject(s)
Animals , Apoptosis , Blotting, Western , Brain , Brain Ischemia , Brain-Derived Neurotrophic Factor , Carotid Artery, Common , Caspase 3 , Cell Proliferation , Cytochromes c , Exercise Test , Exercise , Gerbillinae , Hippocampus , Immunohistochemistry , Ischemia , Kidney Failure, Chronic , Memory , Models, Animal , Nervous System Diseases , Neurons , Stroke , Urinary Tract , Urinary Tract InfectionsABSTRACT
44.1%)(P < 0.05).5. A higher survival rate was seen in patients of tongue cancer with higher differenciation grade (P < 0.05).6. It is well known that drinking and smoking have great influence on the survival rate of patients of squamous cell carcinoma of tongue. But these was no statistical significance.CONCLUSION: The overall 5-year survival rate of tongue cancer was 67.0% and it was mostly influenced by factors like age, pTNM stage, cervical lymph node metastasis, differentiation of cancer cell etc.
Subject(s)
Humans , Male , Carcinoma, Squamous Cell , Drinking , Lymph Nodes , Neoplasm Metastasis , Prognosis , Smoke , Smoking , Survival Rate , Tongue , Tongue NeoplasmsABSTRACT
Subject(s)
Female , Humans , Male , Body Mass Index , Carcinoma, Squamous Cell , Cheek , Gingiva , Lip , Lymph Nodes , Mouth , Mouth Floor , Mouth Neoplasms , Neoplasm Metastasis , Palate , Prevalence , Prognosis , Recurrence , Retrospective Studies , Smoke , Smoking , Survival Rate , TongueABSTRACT
Subject(s)
Humans , Cleft Palate , Deglutition , Free Tissue Flaps , Mouth , Nasal Cavity , Palate, Soft , Tissue Donors , Velopharyngeal InsufficiencyABSTRACT
PURPOSE: Cerebral ischemia leads to neuronal cell death, and eventually causes neurological impairments. Tadalafil is a long-acting phosphodiesterase type-5 (PDE-5) inhibitor, and it has been used for the treatment of erectile dysfunction. In the present study, we investigated whether tadalafil has the protective effect on apoptotic neuronal cell death in the motor cortex following transient global ischemia in gerbils. MATERIALS AND METHODS: For this study, Mongolian gerbils were used for the experimental animals, and transient global ischemia was induced to the gerbils by occlusion of both common carotid arteries for 7 min. Gerbils were randomly divided into five groups (n=8 in each group): the sham-operation group, the cerebral ischemia-induced group, the cerebral ischemia-induced and 0.1 mg/kg tadalafil-treated group, the cerebral ischemia-induced and 1 mg/kg tadalafil-treated group, the cerebral ischemia-induced and 10 mg/kg tadalafil-treated group. Tadalafil-treated groups received tadalafil orally once a day for a 7 consecutive days, starting one day after surgery. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and immunohistochemistry for caspase-3 were performed for the detection of apoptotic neuronal cell death in the motor cortex. RESULTS: The number of TUNEL-positive cells was 21.45+/-3.69/section in the sham-operation group, 771.66+/-97.25/section in the cerebral ischemia-induced group, 688.44+/-81.35/section in the cerebral ischemia-induced and 0.1 mg/kg tadalafil-treated group, 295.66+/-36.34/section in the cerebral ischemia-induced and 1 mg/kg tadalafil-treated group, and 198.47+/-25.25/section in the cerebral ischemia-induced and 10 mg/kg tadalafil-treated group. In the present results, induction of ischemic injury increased apoptotic neuronal cell death in the motor cortex of gerbils. However, tadalafil treatment suppressed the cerebral ischemia-induced apoptotic neuronal cell death in the motor cortex as dose-dependently. CONCLUSIONS: Here in this study, we showed that tadalafil has protective effect on the cerebral ischemia-induced apoptotic neuronal cell death, and thus this drug may facilitate the recovery following ischemic cerebral injury.
Subject(s)
Animals , Male , Apoptosis , Brain Ischemia , Carbolines , Carotid Artery, Common , Caspase 3 , Cell Death , Erectile Dysfunction , Gerbillinae , Immunohistochemistry , Ischemia , Motor Cortex , Neurons , Polyenes , TadalafilABSTRACT
The MHC class II transactivator (CIITA) is the master transcriptional regulator of genes involved in MHC class II restricted antigen presentation. Previously we suggested another role of CIITA in Th1/Th2 balance by demonstrating that forced expression of CIITA in murine T cells repressed Th1 immunity both in vitro and in vivo. However, the results were contradictory to the report that CIITA functioned to suppress the production of Th2 cytokine by CD4+T cells in CIITA deficient mice. In this study, we investigated the influence of constitutive expression of CIITA in T cells on Th2 immune response in vivo using murine experimental colitis model. In the dextran sodium sulfate-induced acute colitis, a disease involving innate immunity, CIITA transgenic mice and wild type control mice showed similar progression of the disease. However, the development of oxazolone-induced colitis, a colitis mediated by predominantly Th2 immune response, was aggravated in CIITA-transgenic mice. And, CD4+T cells from the mesenteric lymph node of CIITA-transgenic mice treated with oxazolone exhibited a high level of IL-4 secretion. Together, these data demonstrate that constitutive expression of CIITA in T cells skews immune response to Th2, resulting in aggravation of Th2-mediated colitis in vivo.
Subject(s)
Mice , Animals , Trans-Activators/physiology , Th2 Cells/immunology , T-Lymphocytes/metabolism , Oxazolone/pharmacology , Nuclear Proteins/physiology , Mice, Transgenic , Mice, Inbred C57BL , Interleukin-4/biosynthesis , Colitis/etiologyABSTRACT
We examined the effect of class II transactivator (CIITA) down-modulation on allograft rejection. To inhibit the function of CIITA, we constructed a series of CIITA mutants and found one exhibiting the dominant-negative effect on the regulation of major histocompatibility complex (MHC) class II expression. To test whether the CIITA dominant-negative mutant reduces immunogenecity, CIITA-transfected melanoma cells were injected into allogeneic host and assessed for immune evading activity against host immune cells. We demonstrated that the CIITA dominant-negative mutant allowed tumor nodules to develop earlier in the lung than control by this tumor challenge study. Furthermore, skin grafts deficient for CIITA also survived longer than wild-type in allogeneic hosts. Both the tumor challenge and skin graft studies suggest the inhibition of CIITA molecules in donor tissue would be beneficial to the control of allo-response.
Subject(s)
Mice , Male , Humans , Animals , Transplantation, Homologous , Transfection , Trans-Activators/genetics , Transcriptional Activation/genetics , Skin Transplantation , Nuclear Proteins/genetics , Mutation , Mice, Transgenic , Mice, Knockout , Mice, Inbred C57BL , Mice, Inbred BALB C , Melanoma, Experimental/genetics , Interferon-gamma/pharmacology , Histocompatibility Antigens Class II/genetics , Graft Survival/genetics , Graft Rejection/genetics , Genes, MHC Class II/genetics , Flow Cytometry , DNA, Complementary/genetics , Cell Proliferation/drug effects , Cell Line, TumorABSTRACT
BACKGROUND: Major burn injury causes aberrant responses to neuromuscular blocking agents, and an increase in fetal type nicotinic acetylcholine receptors (nAchR) has been speculated to contribute to the altered response. This study was conducted to test the hypothesis that the increases in nAchR are due to generalized systemic effects, not limited to area of burn in humans. Using the rectus abdominis muscle of the burned area and quadriceps muscle of nonburned area from the single major burn patient, the changes of nAchR subunits of alpha1, gamma and alpha7 were compared. METHODS: Twelve adults (M:F = 11:1) with total body surface area (TBSA) of 48.8 +/- 19.3% major burns, undergoing burn related elective surgery, were included at 30.8 +/- 16.4 days after the burn injury. Only those with burns in abdominal area and no burns in the lower extremity, were selected. Under general anesthesia, muscle biopsy was taken from the rectus abdominis muscle under the burned abdominal area as well as from the quadriceps muscle under the unburned thigh, at least 30 cm away from the closest burn wound margin. The nAchR changes in the muscles were assayed by western blot using subtype specific mouse antibody for alpha1, gamma and alpha7. RESULTS: The nAchR subunit quantitation (volume% compared to nonburn controls) of alpha1, gamma and alpha7 in the rectus and quadriceps by densitometry were 335.4 +/- 45.4 vs. 321.7 +/- 76.2, 298.3 +/- 234.3 vs. 290.0 +/- 202.3, 149.7 +/- 22.6 vs. 141.6 +/- 35.6, respectively, showing no significant statistical differences between burned and nonburned area (P > 0.05). However, large coefficients of variation were noted in both muscles of gamma group, which may suggest indirect evidence of proliferation of fetal type nAchR in the major burns. TBSA and days after the burn injury were poorly correlated with the amount of expression of subtypes of acetylcholine receptors tested. CONCLUSIONS: Our results confirm that systemic effects of thermal injury include an increase in nAchR at sites distant from the thermal injury, which may account for the skeletal muscle dysfunction and aberrant responses to neuromuscular relaxation. Further studies need to address the importance of burn size and its effects on quantitative and qualitative changes in receptor.
Subject(s)
Adult , Animals , Humans , Mice , Anesthesia, General , Biopsy , Blotting, Western , Body Surface Area , Burns , Densitometry , Lower Extremity , Muscle, Skeletal , Muscles , Neuromuscular Blocking Agents , Quadriceps Muscle , Receptors, Cholinergic , Receptors, Nicotinic , Rectus Abdominis , Relaxation , Thigh , Wounds and InjuriesABSTRACT
BACKGROUND: Early escharectomy has been shown to improve the survival rates and the treatment outcomes of major burn patients. However, its exact mechanism, especially in terms of the human immune system, has not been fully elucidated. This observational study, which placed a focus on adhesion molecules, was conducted to assess changes of soluble intercelluar adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin in major burn patients undergoing early eschar excision. METHODS: Seventeen ASA physical status II or III adult major burn patients, admitted for plastic and reconstructive surgery for burn wound care, were initially recruited. When early escharectomy was scheduled, a series of blood samples were obtained four times at 72 and 24 hours preop and 24 and 72 hours postop, respectively. Changing levels of sICAM-1, sVCAM-1, and E-selectin were measured using quantitative sandwich immunoassay techniques. RESULTS: All patients suffered from major burns. Early escharectomy does not appear to have any significant impact on the levels of sICAM-1 and sVCAM-1. On the other hand, E-selectin levels showed a significant decrease after escharectomy. CONCLUSIONS: Major burn injury certainly induces a systemic inflammatory response. Adhesion molecules behave in such a way that escharectomy has a limited immunomodulatory effect in major burns. This is probably related to the timing and extent of surgery, and the complex nature of burn related inflammation.