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Objective @#To investigate the histological damage recovery of temporomandibular joint condylar cartilage caused by chronic unpredictable moderate stress, aiming to provide an experimental basis for the prevention and treatment of temporomandibular disorder.@*Methods @#This animal experiment was approved by the Laboratory Animal Ethical Inspection, School of Stomatology, The Fourth Military Medical University (No. 2020081). 60 male SD rats were randomly divided into control group, stress group, and 2-, 4- and 8-week post-stress recovery groups. Rats were subjected to chronic unpredictable moderate stress (CUMS) for 8 weeks including damp sawdust for 24 hours, tilted cage for 12 hours, noise for 4 hours, light/dark cycle reversal, water immersion, tail clamp, and restraint stress. The serum assessment, behavioral tests, histological and ultrastructural observation were performed 2-, 4- and 8-weeks after stress factors were removed. Serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were determined with ELISA. The sucrose preference test (SPT) and the forced swim test (FST) were used to assess the depressive-like behavior. The expression level of interleukin-1α (IL-1α) and matrix metalloproteinases-3 (MMP-3) were determined by Immunohistochemistry and Western blot.@*Results @#At the end of 8 weeks of CUMS, the serum levels of CORT and ACTH were significantly higher in stress group compared with control group (P<0.01). The sucrose preference decreased significantly and the immobility time increased significantly in the stressed rats compared with those in the control group, indicating a successful establishment of CUMS. The condylar cartilage showed significant degenerative changes, with disorganized collagen fibers and reduced proteoglycan synthesis on the cartilage surface. IL-1α and MMP-3 were expressed in the intracellular and extracellular matrix of the condylar cartilage, and their expression levels were increased (P<0.01). After 2 weeks of stress removal, the serum levels of CORT and ACTH were decreased but higher than control group (P<0.01), and behavioral changes were still different from the control group (P<0.01); the loosened collagen fibers could still be seen on the surface of condylar cartilage, and some free cell areas were visible within the proliferative layer; additionally, IL-1α and MMP-3 expression in the condyle was reduced in all layers of cartilage when compared with the stress group, but was still higher than in the control group (P<0.01). After 4 weeks of stress removal, the serum levels of CORT and ACTH changes returned to normal levels and behavioral changes were still different from control group (P<0.05); a few collagen fibers could be seen on the surface of the condylar cartilage and the expressions of IL-1α and MMP-3 decreased significantly compared with the stress group (P<0.01), with the similar level of IL-1α (P>0.05) and higher expression of MMP-3 comparing with the control group (P<0.01). After 8 weeks of stress removal, behavioral changes returned to normal levels, with no statistically significant differences compared with the control group (P>0.05). The condylar collagen fibers increased and showed a corrugated pattern, and no serious subchondral bone damage as well as irreversible damage occurred. Both of the expression levels of IL-1α and MMP-3 approached those of the control group after 8 weeks of stress removal (P>0.05). @*Conclusion@# The behavioral changes and condylar cartilage damage caused by CUMS could be self-repaired. The decline in IL-1α and MMP-3 expression may be one of the intrinsic mechanisms of this self-repair process.
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SUMMARY OBJECTIVE: The aim of this study was to investigate whether platelet parameters and pro-inflammatory cytokines associated with platelet activation could be surrogate markers of the diabetic retinopathy stages in type 2 diabetic patients. METHODS: This prospective case-control study included 108 type 2 diabetes mellitus patients and 48 healthy controls. After fundoscopic examination, patients were divided into three groups: no retinopathy, nonproliferative diabetic retinopathy, or proliferative retinopathy. Platelet selectin, interleukin-1alpha, and interleukin-6 values were measured by the enzyme-linked immunosorbent assay method. Homeostatic Model Assessment for Insulin Resistance formula was used to assess insulin resistance in patients. RESULTS: Mean platelet volume was lower and interleukin-1alpha was higher in the patients compared to the healthy controls (p=0.046 and p<0.001, respectively). In addition, a positive correlation between the platelet distribution width and HbA1C levels was observed in the patients (r=0.334, p<0.001). CONCLUSION: In the studies evaluating the utility of platelet indices and the associated cytokines in diabetic retinopathy, there is a need for the standardization of the measurements. All medications that can affect platelet activation should be taken into consideration.
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Objective:To investigate the effect of resveratrol on the expression of inflammatory cytokines and related genes in human SZ95 sebocytes induced by benzo (a) pyrene.Methods:Human SZ95 sebocytes were cultured in vitro, and divided into 4 groups: control group treated with 1‰ dimethyl sulfoxide for 27 hours, resveratrol group treated with 1 × 10 -5 mol/L resveratrol for 24 hours, benzo (a) pyrene group treated with 1 × 10 -5 mol/L benzo (a) pyrene for 3 hours, resveratrol+benzo (a) pyrene group treated with 1 × 10 -5 mol/L resveratrol for 24 hours followed by 1 × 10 -5 mol/L benzo (a) pyrene for 3 hours. Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of interleukin (IL) -1α, IL-6, aryl hydrocarbon receptor (AhR) , cytochrome P4501A1 (CYP1A1) and cytochrome P4501B1 (CYP1B1) in SZ95 sebocytes in the above groups; Western blot analysis was conducted to determine the phosphorylation level of p38 mitogen-activated protein kinase (p38 MAPK, expressed as the ratio of phosphorylated to total p38 MAPK) and AhR protein expression; enzyme-linked immunosorbent assay (ELISA) was conducted to detect levels of IL-1α and IL-6 in the cell culture supernatant in each group. One-way analysis of variance was used for comparison of means among multiple groups, and least significant difference- t test was used for multiple comparisons. Results:The mRNA and protein expression of IL-1α in SZ95 sebocytes significantly differed among the control group, resveratrol group, benzo (a) pyrene group and resveratrol+benzo (a) pyrene group (mRNA: 2.045 ± 0.272, 2.058 ± 0.154, 3.124 ± 0.094, 2.185 ± 0.337, protein: 9.132 ± 1.181, 9.429 ± 0.771, 20.361 ± 0.907, 9.917 ± 0.897, F=14.662, 101.705, P < 0.01, < 0.001, respectively) , and were significantly lower in the resveratrol+benzo (a) pyrene group than in the benzo (a) pyrene group (both P < 0.01) . In addition, the phosphorylation level of p38 was significantly higher in the benzo (a) pyrene group than in the control group, resveratrol group and resveratrol+benzo (a) pyrene group ( F=303.129, P < 0.000 1) . The mRNA expression of AhR, CYP1A1 and CYP1B1 was significantly lower in the resveratrol+benzo (a) pyrene group than in the benzo (a) pyrene group ( t=10.64, 33.599, 18.327, respectively, all P < 0.001) . The benzo (a) pyrene group showed significantly decreased protein expression of AhR compared with the resveratrol+benzo (a) pyrene group ( P < 0.001) . Conclusion:Resveratrol can inhibit the environmental pollutant benzo (a) pyrene-induced expression of inflammatory factor IL-1α in SZ95 sebocytes, which is likely mediated by the AhR and p38MAPK pathways.
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@#Introduction: Ameloblastoma is a benign but locally invasive odontogenic epithelial neoplasm with a high recurrence rate after treatment. The two main subsets encountered clinically are unicystic (UA) and solid/multicystic ameloblastoma (SMA). Currently neoplastic progression of many tumour types are believed to be related to parenchyma-stromal cell-cell interactions mediated by cytokines notably interleukins (IL). However their roles in ameloblastoma remain ill-understood. Materials and Methods: Thirty-nine formalin-fixed paraffin-embedded ameloblastoma cases comprising unicystic ameloblastoma (n=19) and solid/multicystic ameloblastoma (n=20) were subjected to IHC staining for IL-1α, IL-1β, IL-6 and IL-8. A semi-quantitative method was used to evaluate the expression levels of these cytokines according to cell types in the tumoural parenchyma and stroma. Results: Major findings were upregulations of IL-1α and IL-6 in SMA compared to UA. Both cytokines were heterogeneously detected in the tumoural parenchyma and stroma. Within the neoplastic epithelial compartment, IL-1α expression was more frequently detected in PA-like cells in UA whereas it was more frequently encountered in SR-like cells in SMA. IL-6 demonstrated higher expression levels in the stromal compartment of SMA. IL-1β and IL-8 were markedly underexpressed in both tumour subsets. Conclusions: Overexpression of IL-1α in SMA suggests that this growth factor might play a role in promoting bone resorption and local invasiveness in this subtype. The expression levels of IL-1α and IL-6 in three cellular localizations indicate that parenchymal-stromal components of ameloblastoma interact reciprocally via IL-1α and IL-6 to create a microenvironment conducive for tumour progression.
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Objective To detect the changes of (interleukin, IL) -1α, IL-1β and IL-13 mRNA in lung tissue and serum of drown rats, and to explore the potential value for the diagnosis of drowning in forensic practice. Methods Eighteen SD rats were randomly divided into drowning group, blank control group and myocardial infarction group (as control group). The serum of right ventricular, the inferior lobe of right lung and the myocardium were taken from the rats in different groups. The expressions of IL-1α, IL-1β and IL-13 mRNA in the lung tissue and the serum of right ventricular were detected by TaqMan probe method. Results The expression differences of IL-1α, IL-1β and IL-13 mRNA in lung tissue between drowning group and blank control group, myocardial infarction group were not statistically significant (P>0.05). The expression of IL-1β and IL-13 mRNA in serum of right ventricular increased (P<0.05). The expression differences of IL-1α, IL-1β and IL-13 mRNA in serum between blank con-trol group and myocardial infarction group were not statistically significant (P>0.05). Conclusion The changes of cytokines IL-1β and IL-13 mRNA in the serum of right ventricular of drown rats are statis-tical significance, which are highly correlated with drowning.
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BACKGROUND:Numerous studies have shown that local lumbar stenosis can cause immunological abnormalities and local chronic inflammation, which is the main cause of pain. At present, studies on inflammatory factors and lumbar spinal stenosis mainly focused on intervertebral discs, facet joint and ligamenta flava. No reports addressed the relationship between inflammatory factor in vein of lumbar spinal canal and lumbar spinal stenosis. OBJECTIVE:To analyze the correlation of serum interleukin-1αand tumor necrosis factor-αlevels with lumbar spinal stenosis. METHODS:A total of 51 patients with lumbar spinal stenosis or lumbar vertebral burst fracture, who underwent posterior lumbar decompression in the Department of Spine Surgery, Shanghai East Hospital, Tongji University in China from September 2011 to December 2013, were enrol ed in this study. Visual analogue scale score of low back pain and Oswestry disability index were evaluated before treatment. Peripheral vein blood and venous blood in the vertebral canal were col ected from patients with lumbar spinal stenosis or lumbar vertebral burst fracture. The concentrations of serum interleukin-1αand tumor necrosis factor-αwere determined using enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION:The concentration of interleukin-1αin degenerative lumbar stenosis group was significantly higher than that in the lumbar burst fracture group and peripheral veins (P<0.05). The more segments of lumbar spinal stenosis, the higher the venous serum interleukin-1αlevels were in the degenerative lumbar stenosis group, but the statistical difference was not significant. Linear correlation analysis results displayed that interleukin-1αlevels were positively associated with low back pain and disability scores in the degenerative lumbar stenosis group (r2=0.359 3, P<0.05;r2=0.526 4, P<0.05). These results indicated that the lumbar spinal venous inflammatory factors may be one of the reasons of low back pain and dysfunction in patients with degenerative lumbar spinal stenosis.
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@#Objective To investigate the effects of electrical stimulation on the expression of glial fibrillary acidic protein (GFAP) andinterleukin-1 alpha (IL-1α) in adult rats with spinal cord injury. Methods 72 adult SD rats were randomly divided into damage group (n=24), electrical stimulation group (n=24) and normal group (n=24). The spinal cord incomplete injury model on T9 was made with Allen'smethod in the former 2 groups. The rats in electrical stimulation group accepted electrical stimulation for 7 d. All the rats were evaluatedwith the Basso, Beattie & Bresnahan locomotor rating scale (BBB scale), and the expression of GFAP and IL-1α were determined with immunohistochemistry.Results The BBB scores in both the damage group and electrical stimulation group were significantly less than that inthe normal group (P<0.05), and it was more in the electrical stimulation group than in the damage group 5 and 7 d after injury. The expressionsof the GFAP significantly increased after injury to the peak on 5th day, while it was less in the electrical stimulation group than in thedamage group 5 and 7 d after injury (P<0.05). The expressions of the IL-1α increased continually after injury, while it was less in the electricalstimulation group than in the damage group 5 and 7 d after injury (P<0.05). Conclusion Electrical stimulation can inhibit the expressionof GFAP and IL-1α, that reduce inflammation and glial scar formation.
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STUDY DESIGN: An experimental animal study. OBJECTIVES: To create a more appropriate disc degeneration model which shows how Interleukin 1alpha may induce the activation of metalloproteinases within the nucleus pulposus. SUMMARY OF LITERATURE REVIEW: There are few disc degeneration models wherein there is activation of metalloproteinases within the nucleus pulposus without structural destruction of the intervertebral disc. MATERIALS AND METHODS: Three consecutive intervertebral discs in New Zealand White Rabbits were exposed. Each disc was injected with 0.1ml of saline (Saline group), 0.1ml of 1microg/ml (IL-1 group), 0.1ml of 10microg/ml (IL-10 group) of IL-1alpha through a 30-gauge needle. The lumbar spine was harvested 12 weeks after operation. We then analyzed radiographic findings and histological changes. RESULTS: There was no difference in the radiological disc height index among the three groups; 0.071 in saline group, 0.045 in IL-1 group and 0.058 in IL-10 group (p=0.194). The histological cellularity of the nucleus pulposus revealed a decrease in the number of cells (p=0.0001, 1.42 in saline group vs. 3.00 in IL-10 group; p=0.001, 2.00 in IL-1 group and 3.00 in IL-10). The histological matrix of the nucleus pulposus was 1.42 in saline group and 2.42 in IL-10(p=0.007), which meant that there had been condensation of the extracellular nucleus pulposus matrix. CONCLUSIONS: The results of this study demonstrate that interleukin-1alpha may contribute to degradation of the nucleus pulposus. This is useful for future study into the effects of the cytokine inhibitor on matrix regeneration and cellularity in the nucleus pulposus in intervertebral disc disease.
Subject(s)
Animals , Humans , Rabbits , White People , Interleukin-1 , Interleukin-10 , Interleukin-1alpha , Intervertebral Disc , Intervertebral Disc Degeneration , Intervertebral Disc Displacement , Metalloproteases , Needles , Regeneration , SpineABSTRACT
BACKGROUND/AIMS: For unknown reasons, caspase-1 -/- mice, protected against cisplatin-induced acute renal failure (ARF), are deficient in interleukin (IL)-1alpha. We thus asked whether IL-1alpha deficiency underlies the mechanism of protection against cisplatin-induced ARF in these mice. METHODS: Cisplatin (30 mg/kg) was injected intraperitoneally into wild-type C57BL/6 mice to produce a cisplatin-induced model of ARF. IL-1alpha was measured in control vehicle- and cisplatin-treated wild-type animals. We also examined whether IL-1alpha -/- mice were similarly protected against cisplatin-induced ARF. Additionally, infiltration of CD11b- and CD49b-positive cells, as markers of macrophages, natural killer, and natural killer T cells (pan-NK cells), was investigated in wild-type and IL-1alpha -/- mice. RESULTS: Compared with vehicle-treated mice, renal IL-1alpha increased in cisplatin-treated wild-type mice beginning on day 1. IL-1alpha -/- mice were shown to be protected against cisplatin-induced ARF. No significant difference in the infiltration of neutrophils or CD11b- and CD49b-positive cells were observed between wild-type and IL-1alpha -/- mice. CONCLUSIONS: Mice deficient in IL-1alpha are protected against cisplatin-induced ARF. The lack of IL-1alpha may explain, at least in part, the protection against cisplatin-induced ARF observed in caspase-1 -/- mice. Investigation of the protective mechanism (s) in IL-1alpha -/- mice in cisplatin-induced ARF merits further study.
Subject(s)
Animals , Mice , Acute Kidney Injury/chemically induced , CD11b Antigen/analysis , Apoptosis , Biomarkers/blood , Blood Urea Nitrogen , Cisplatin , Creatinine/blood , Disease Models, Animal , Fluorescent Antibody Technique , Integrin alpha2/analysis , Interleukin-1alpha/deficiency , Kidney/immunology , Killer Cells, Natural/immunology , Macrophages/immunology , Mice, Inbred C57BL , Mice, Transgenic , Natural Killer T-Cells/immunology , Necrosis , Neutrophil Infiltration , Time FactorsABSTRACT
BACKGROUND: One of the limitation during the irradiation of malignant tumor is hazard to normal tissue although it is important and effective tool for treating malignant tumor. We studied the role of interleukin-1 alpha (IL-1alpha) and interleukin-6 (IL-6) in the radiation-induced lung injury especially on fibrosis. METHODS: We irradiated right-side lungs of thirty Sprague-Dawley rats with single fraction of 20 Gy and then sacrificed the animals until 20th week at intervals of two weeks. Both irradiated and unirradiated lung tissues were stained hematoxilin and eosin, Masson trichrome, reticulin and immunohistochemical staining for IL-1alpha and IL-6. The degree of the staining for IL-1alpha and IL-6 were examined semiquantitatively. RESULTS: Two weeks after irradiation interstitial edema and capillary congestion appeared, followed by increase of the monocytes infiltration and proteinaceous material during 4th and 8th week. After eight weeks of irradiation, collagen and reticulin fibers were detected along alveolar wall. 12th to 20th week, fibrosis in interstitium, decreased number of alveoli and thickening of bronchial wall were observed. The degree of immunohistochemical staining for IL-1alpha and IL-6 was increased rapidly during the first three week and then decreased slowly, but remain incresed until 20th week. CONCLUSION: Our Study demonstrate the early and persistent elevation of cytokines IL-1alpha and IL-6 by immunohistochemical stain in rat lung following pulmonary irradiation. We think cytokines are produced immediately after irradiation, make collagen genes turn on and perisist until the expression of late effects become apparent pathologically and clinically.
Subject(s)
Animals , Rats , Capillaries , Collagen , Cytokines , Edema , Eosine Yellowish-(YS) , Estrogens, Conjugated (USP) , Fibrosis , Interleukin-1 , Interleukin-1alpha , Interleukin-6 , Lung Injury , Lung , Monocytes , Rats, Sprague-Dawley , ReticulinABSTRACT
BACKGROUND: The Fas antigen is a cell surface molecule that mediates apoptosis in many cell types. Matsues group indicated that keratinocytes constitutively express the Fas antigen and apoptosis was induced only on pretreatment with interferon-r (IFN-y) in cultured normal human keratinocytes (NHK). OBJECTIVE: We undertook this study to determine the induction of apoptosis by Fas antibody alone and/or in combination with IFN y, IL-1a in normal human keratinocytes (NHK) and transitional epithelioma cell lines (KB cell) which had lower levels of intracellular IL-1 receptor antago- nists (IL-1ra ). METHODS: We used cultured NHK and KB cells. Each cell was treated with IFN-r, IL-la and Fas antibody for induction of apoptosis. For quantifying the apoptosis, index fluorescent DNA- binding dyes were used. Result: Fas antibody alone could induce apoptosis not only in KB cells but also in NHK cells. The combination of Fas antibody and IFN-r enhanced the induction of apoptosis in NHK and KB cells. The IL-la alone could induce apoptosis only in KB cells which had relatively small amounts of IL-1ra compared to NHK. CONCLUSION: Our result may indicate that Fas antigen in human keratinocytes can regulate normal epidermal cellular differentiation and proliferation.
Subject(s)
Humans , fas Receptor , Apoptosis , Carcinoma , Cell Line , Coloring Agents , Interleukin 1 Receptor Antagonist Protein , Interleukin-1 , Interleukin-1alpha , KB Cells , KeratinocytesABSTRACT
BACKGROUND: Interleukin-1alpha is interesting lymphokine to cardiologists because it has been implicated as a regulatory protein in the development and clinical sequale of atherosclerosis, including the modulation of low density lipoprotein metabolism, the regulation of vascular smooth muscle cell mitogenesis, the stimulation of leukocyte adherence to endothelium, and procoagulant activity. But most interleukin-1alpha remains in the cytosol of cells in its precursor form, and is transported to cell surface. and associated with cell membrane. Therefore considerable amount of interleukin-1alpha, contrast to interleukin-1beta, is not released by cells into the extracellular space and the circulation. Despite of increased production of interleukin-1alpha, circulating level may not be elevated because of autocrine and paracrine action of that. In order to elucidate whether interleukin-1alpha is systematically elevated or not in patients with coronary artery disease who are complaining of chest pain, we undertook this study. METHODS: We isolated lymphocytes from peripheral blood in patients and control group. After the peripheral lymphocytes were cultured in the presence or absence of phytohemmagglutinin in RPMI-1640 media for 24 hours, we measured the content of interleukin-1alpha in supernatant by radioimmunoassay. RESULTS: 1) In the absence of phytohemagglutinin, the mean value of Interleukin-1alpha in the supernatant was 29.13+/-17.42 pmol/ml in control group and 27.28+/-18.80 pmol/ml in patients group(p=NS). 2) In the presence of phytohemagglutinin, the mean value of Interleukin-1alpha in the supernantant was 36.53+/-20.72 pmol/ml in control group and 152.13+/-91.85 pmol/ml in patient group(p<0.0001). CONCLUSION: Significant increase of interleukin-1alpha in the presence of phytohemagglutinin in the patient group means that the peripheral lymphocytes in patients with coronary artery disease are activated to produce interleukin-1alpha.