Relationship between Th1/Th2 balance and CD28/CTLA-4 expression on peripheral blood T cells in patients with systemic lupus erythematosus

AIM: To investigate the pattern of Th1/Th2 balance in systemic lupus erythematosus(SLE) patients and the relationship between CD28/CTLA-4(cytotoxic T-lymphocyte antigen-4) molecule expression and Th1/Th2 balance.METHODS: Eighteen SLE patients met the ARA 1997 updated SLE criteria were selected in the study. According to Bombardier's SLEDAI criteria, all patients were classified into two groups: active group(12 cases) and static group(6 cases). Fourteen normal individuals, matched for age and sex of the patients, served as controls. The peripheral blood mononuclear cells(PBMCs) were isolated by density gradient centrifugation and cultured in RPMI-1640 culture medium. After treated with PMA(5 μg/L) and ionomycin(500 μg/L) for 72 h, the PBMCs were collected, the contents of IFN-γ and IL-10 in the supernatant of cultured PBMCs were detected using enzyme linked immunosorbent assay(ELISA). The expression of CD28 and CTLA-4 molecules on T cells were detected by flow cytometric technique with double staining by FITC or PE labeled monoclonal antibodies. RESULTS: The level of IL-10 was higher in the PBMCs of active and static SLE patients(351.29 ng/L±153.31 ng/L and 319.37 ng/L±153.39 ng/L) than that in controls(254.48 ng/L±120.69 ng/L), but the difference did not reach statistical significance(P>0.05). The level of IFN-γ was significantly lower in the PBMCs of active SLE patients(25.76 ng/L±16.09 ng/L) than that in controls(50.71 ng/L±27.92 ng/L, P＜0.05). The ratio of IL-10/IFN-γ was significantly higher in active SLE patients(18.74±13.77) than that in controls(6.66±4.95, P<0.05). Either before or after culture, the expression of CD28 molecule on CD3⁺and CD8⁺ T cells from all SLE patients was not remarkably different from that in the cells of controls. Before culture, the expression of CTLA-4 molecule on CD3⁺T cells of active SLE patients(0.79%+0.37%) was significantly lower than that in the cells of controls(1.31%+0.61%, P<0.05). After culture, the expression of CTLA-4 molecule on CD3⁺ T cells of SLE patients was still lower than that in the cells of normal controls without statistical significance(P＞0.05).The expression level of CD28 molecule on CD3⁺ or CD8⁺ T cells in active SLE patients and controls was not correlated with the levels of IFN-γ and IL-10 in the supernatants(P＞0.05). The level of CTLA-4 molecule expression on CD3⁺ T cells of active SLE patients was positively correlated with IFN-γ level(r=0.681, P<0.05), while was negatively correlated with IL-10 levels(r=-0.624,P＜0.05) and the ratio of IL-10/IFN-γ(r=-0.738, P<0.01). The level of CTLA-4 molecule expression on CD3⁺ or CD8⁺ T cells of controls showed no correlation with IFN-γ levels, while showed negative correlations with IL-10 level(r=-0.587, P<0.05; r=-0.563, P<0.05, respectively).CONCLUSION: There is a bias in the differentiation of Th0 cells towards Th2 in SLE patients. CTLA-4 probably plays an important role in this mechanism through suppressing the signal transmitted by CD28.     

Changes of arachidonic acid and TNF-α in primary glomerular disease

AIM: To explore the changes of arachidonic acid (AA) and tumor necrosis factor α(TNF-α) in primary glomerular disease and their effects on oxidative stress. METHODS: Fifty-five patients with primary glomerular disease confirmed by clinical examination and renal biopsy were selected. The patients were divided into 3 groups according to their glomerular filtration rate as chronic kidney disease(CKD)1,2 group, CKD3,4 group, and CKD5 group. The levels of free AA, TNF-α, malondialdehyde(MDA) and high-sensitive C-reactive protein(hs-CRP) in serum were detected by ELISA. RESULTS: No significant difference of AA and MDA between CKD1,2 group and CKD3,4 group was observed (P>0.05). The level of AA was obviously higher, and the level of MDA was significantly lower in CKD5 group than those in the other groups (P<0.05). No difference of TNF-α concentration between CKD3,4 group and CKD5 group was found (P>0.05), but that was significantly lower than that in CKD1,2 group (P<0.05). The content of hs-CRP in each group was not different (P>0.05). The level of MDA was negatively correlated with the level of AA (r=-0.752,P<0.01), whereas positively correlated with the level of TNF-α (r=0.463, P<0.01). The multiple linear regression equation of MDA(Y) for AA(X₁) and TNF-α(X₂) was Y=1 361.723-2.661X₁+9.320X₂ (F=52.445, P<0.01). CONCLUSION: AA and TNF-α are the important factors that influence the level of oxidative stress in primary glomerular disease. AA inhibits and TNF-α promotes oxidative stress.     

Change of serum CXC chemokine ligand 16 in gout patients and its clinical significance

AIM: To explore the relationship between the changes of serum CXC chemokine ligand 16 (CXCL16) and the loss of kidney functions in chronic gout patients and its clinical significance. METHODS: Twenty gout patients with chronic kidney disease (CKD), 22 gout patients without CKD and 22 CKD subjects were recruited into the present study, while 20 normal age-and sex-matched subjects were assigned into the control group. Serum level of CXCL16 and other relevant clinical and biochemical parameters in all subjects were obtained upon standard clinical examinations. Ceatinine clearance rate (CCR) and estimated glomerular filtration rate (eGFR) were calculated based on the clinical parameters. To analyze the clinical data, student's unpaired t-test was used for the comparison between 2 groups. One-way ANOVA assay and multiple stepwise regression were used for multiple groups.RESULTS: Serum level of CXCL16 was significantly increased in gout subjects compared with the healthy control and CKD subjects (P<0.05). Serum level of CXCL16 in gout patients with CKD was significantly higher than that in gout patients without CKD (P<0.05). Furthermore, the mRNA expression of CXCL16 in peripheral blood mononuclear cells (PBMC) of gout patients was significantly higher than that in healthy subjects. Multiple stepwise regression analysis indicated that serum CXCL16 was independently associated with 24 h urine protein, CCR and C-reactive protein (P<0.05). CONCLUSION: Serum CXCL16 level in gout patients is associated with the change of renal functions. Elucidating the pathophysiologcial mechanism of CXCL16 in gout patients requires further study.     

Effect of Xingnao enema fluid on brain injury and IL-33/ST2 signaling pathway in rats after cardiopulmonary resuscitation

AIM: To study the effects of Xingnao enema fluid on brain injury and IL-33/ST2 signaling pathway in rats after cardiopulmonary resuscitation, and to explore the brain protective effect and mechanism of Xingnao enema fluid. METHODS: SD rats were randomly divided into sham operation group, model group, low-dose (5 mL/kg), middle-dose (10 mL/kg) and high-dose (20 mL/kg) Xingnao enema liquid groups, and ulinastatin group, with 12 rats in each group. Except for the rats in sham operation group, the rats in other groups were used to establish the model of cardiopulmonary resuscitation and were treated with Xingnao enema fluid and ulinastatin. Seven days later, all rats were scored for neurological deficit. The rats were sacrificed, and the water content of brain tissues was calculated. Hematoxylin-eosin (HE) staining was used to detect the pathological changes of brain tissues of the rats in each group. The levels of super-oxide dismutase (SOD) and malondialdehyde (MDA) were detected in the brain tissue. The levels of S100 calcium bin-ding protein beta subunit (S100β) and neuron-specific enolase (NSE) in serum, and interleukin (IL)-1β and tumor necrosis factor (TNF)-α in brain tissue were measured by ELISA. The expression of interleukin-33 (IL-33) and growth stimulation expressed gene 2 (ST2) in brain tissue was determined by Western blot. RESULTS: Compared with sham operation group, the brain tissue of model group showed tissue disorder, focal hemorrhage, neuronal nucleus contraction, apoptosis and other pathological changes, and the neurological deficit score was increased. The water content of brain tissue, the le-vels of S100β, NSE, MDA, IL-1β, TNF-α, IL-33 and ST2 were significantly increased, and the level of SOD decreased significantly (P<0.05). Compared with model group, the pathological damage of brain tissue in low-, middle- and high-dose Xingnao encma fluid groups and ulinastatin group was reduced, and the neurological deficit score was decreased. The water content of brain tissue, levels of S100β, NSE, MDA, IL-1β, TNF-α, IL-33 and ST2 were significantly decreased, and the level of SOD was increased significantly (P<0.05). There was a dose-dependent relationship in different doses of Xingnao enema fluid groups, and no significant difference between high-dose Xingnao enema fluid group and ulinastatin group was observed (P>0.05). CONCLUSION: Xingnao enema fluid repairs brain injury in rats after cardiopulmonary resuscitation, and down-regulation of IL-33/ST2 signaling pathway may be its mechanism.     

Relationship between Th17/Treg cells and microinflammatory state in uremia patients

AIM: To investigate the changes of T-helper 17(Th17) and regulatory T (Treg) cells in uremic patients by determining the mRNA expression of retinoid-related orphan receptor γt (RORγt)and forkhead box P3 protein (Foxp3), and to observe the correlation with the status of microinflammation. METHODS: Thirty uremia patients enrolled in our blood purification center during July 2010 to July 2011 were selected in the study and divided into maintaining hemodialysis (MHD) group (n=20) and chronic kidney disease (CKD) group (n=10). Twenty matched healthy volunteers served as controls. Serum samples were collected from all the patients in the morning. The mRNA expression of RORγt and Foxp3,plasma interleukin (IL)-6, IL-10 and IL-17 in these patients were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The content of high-sensitivity C-reactive protein (hs-CRP) was detected by immunoturbidimetric assay (ITA). The relationship between the ratio of Treg/Th17 cells and the status of microinflammation was also analyzed. RESULTS: RORγt mRNA, IL-6 and IL-17 were significantly higher in uremia groups than those in control group (P<0.05), while mRNA expression of Foxp3 and the level of plasma IL-10 were significantly lower in uremia group than those in control group (P<0.05). The ratio of RORγt/Foxp3 mRMA was higher in uremia group than that in control group (P<0.05), and no significant difference between MHD group and CKD group was observed. The concentration of hs-CRP, which was higher than 3 mg/L, was significantly higher in uremia group than that in control group (P<0.05). The level of hs-CRP had positive correlation with RORγt, and negative correlation with Foxp3. CONCLUSION: The ratio of Th17 Treg is abnormal in uremia patients. The disequilibrium of Th17 and Treg cells has a close relationship with the status of microinflammation.     

Effect of pachyman polysaccharides on Th17/Treg balance in systemic lupus erythematosus patients

AIM: To investigate the immunomodulatory effect of pachyman polysaccharides (PPS) on T helper 17 cell (Th17)/regulatory T cell (Treg) balance in the peripheral blood of systemic lupus erythematosus (SLE) patients. METHODS: The CD4⁺ T cells were isolated from the peripheral blood samples obtained from 45 SLE patients and 35 healthy controls enrolled in our study using magnetic bead separation method. The proportions of Th17 and Treg cells were measured by flow cytometry. The CD4⁺ T cells from SLE patients and healthy controls were treated with PPS. The cytoto-xicity of PPS was evaluated by detecting cell viability with MTT assay. The contents of interleukin-17 (IL-17), IL-6, IL-10 and transforming growth factor-β (TGF-β) were measured by ELISA. The expression of retinoid-related orphan receptor γt (RORγt) and forkhead box protein P3 (Foxp3) at mRNA and protein levels was determined by RT-qPCR and Western blot, respectively. RESULTS: The Th17 cells were significantly elevated, while Treg cells were obviously decreased in the SLE patients compared with the healthy control group (P<0.05). Compare with control group, the contents of IL-17 and IL-6 were decreased, while the contents of IL-10 and TGF-β were increased (P<0.05). The expression of RORγt at mRNA and protein levels was down-regulated and the expression of Foxp3 was up-regulated (P<0.05). The ratio of Th17/Treg was decreased in 100 μg/L nontoxic PPS-treated CD4⁺ T cells isolated from the SLE patients (P<0.05). CONCLUSION: PPS treatment inhibits Th17 cells and elevates Treg cells in the CD4⁺ T cells isolated from SLE patients, which may have a therapeutic effect on SLE patients.     

Increased expression of CD40 ligand by peripheral blood mononuclear cells in patients with systemic lupus erythematosus

AIM:To investigate expression and function of CD40 ligand by peripheral blood mononuclear cells (PBMCs) in patients with systemic lupus erythematosus (SLE).METHODS:Expression of CD40 ligand by PBMCs in patients with SLE and control were examined by flow cytometric analysis before and after stimulated by phytohemagglutinin(PHA)and depressed by Dexamethasone(Dex). The correlation between expression of CD40 ligand and SLE activity index(SLEDAI) was analysed in patients with SLE.RESULTS:The expression of CD40 ligand by PBMCs in patients with active SLE was higher than that in patients with inactive SLE and control. Though the expression of CD40 ligang by PBMCs could be stimulated by PHA in three groups, it was the highest in patients with active SLE. Dex depressed the expression of CD40 ligand by PBMCs significantly in patients with SLE, but not in control. There was high positive correlation between expression of CD40 ligand and SLEDAI in patients with active and inactive SLE.CONCLUSION:Increased expression of CD40L by PBMCs in patients with SLE may play an important role in pathogenesis of SLE.     

Effect of protease inhibitor bortezomib on treatment of rheumatoid arthritis by affecting IL-33/ST2 signaling pathway

AIM To investigate the effect of bortezomib， a protease inhibitor， on the treatment of rheumatoid arthritis （RA） and it mechanism， based on interleukin-33 （IL-33）/suppression of tumorigenicity 2 （ST2） signaling pathway. METHODS A total of 40 Wistar rats were randomly divided into 4 groups： control group， model group， and low- and high-dose bortezomib groups， with 10 rats in each group. In addition to control group， the rats in other groups were used to construct RA model. Bortezomib was given intraperitoneally at 0.2 mg/kg and 0.5 mg/kg in low- and high-dose bortezomib groups， respectively， while the rats in control group and model group were injected with the same amount of saline， once a day for 21 d. The general situation of the rats in each group was observed， the swelling degree of the foot was calculated， and the inflammation score was evaluated. HE staining was used to observe the pathological changes of ankle joint. The automatic biochemical analyzer was used to detect blood hemoglobin content， the total number of platelets （PLT）， serum creatinine （SCr） level and blood urea nitrogen （BUN） level. The serum levels of IL-6， tumor necrosis factor-α （TNF-α）， IL-33 and ST2 were measured by ELISA. The protein expression of IL-33 and ST2 in ankle tissues of each group was determined by Western blot. RESULTS On the 7th， 14th and 21th days after modeling， compared with control group， the degree of paw swelling in model group was significantly increased （P<0.05）. Compared with model group， the swelling degree of paw in low- and high-dose groups was decreased （P<0.05）. At the end of administration， compared with control group， the synovial cells in model group were increased and in disorder， with a lot of inflammatory exudates in the articular cavity， and the inflammatory score， the levels of PLT， SCr and BUN， the serum levels of IL-6， TNF-α， IL-33 and ST2， and the protein expression of IL-33 and ST2 in ankle tissues were significantly increased （P<0.05）. Compared with model group， the inflammatory exudates in the articular cavity of the rats in low- and high-dose bortezomib groups were decreased， and the inflammatory score， the levels of PLT， SCr and BUN， the serum levels of IL-6， TNF-α， IL-33 and ST2， and the protein expression of IL-33 and ST2 in ankle tissues were decreased （P<0.05）. CONCLUSION Bortezomib may reduce the inflammation and swelling of the joints in RA rats by regulating the IL-33/ST2 signaling pathway.     

IL-33-modified BMSCs attenuate acute kidney injury induced by sepsis in rats through MyD88

AIM To investigate the effect of interleukin-33 (IL-33)-modified bone marrow mesenchymal stem cells (BMSCs) on sepsis-induced acute kidney injury (AKI) in rats and the expression of myeloid differentiation factor 88(MyD88). METHODS A septic rat model was established by cecal ligation and puncture. The SD rats (n=80) were randomly divided into control group, model group, negative transfection group (transplanting untransfected BMSCs) and IL-33 transfection group (transplanting BMSCs transfected with IL-33), with 20 in each group. Survival rates of the rats within 72 h in the 4 groups were compared. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured before, and 24, 48 and 72 h after transplantation. The kidney pathological damage was observed by HE staining, and the apoptosis of renal cells was detected by TUNEL method 72 h after transplantation. Western blot was used to detect the protein expression levels of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), Toll-like receptor 4 (TLR4) and MyD88. RESULTS The survival rate of the rats in model group was significantly lower than that in control group (P<0.05). The survival rate of the rats in IL-33 transfection group was higher than that in model group and negative transfection group (P<0.05). The levels of SCr and BUN in model group were higher than those in control group (P<0.05). The levels of SCr and BUN in IL-33 transfection group were significantly reduced after transplantation, and were lower than those in model group and negative transfection group (P<0.05). The renal tissue pathological injury score in model group was significantly higher than that in control group (P<0.05). Compared with model group and negative transfection group, the renal tissue pathological injury score in IL-33 transfection group was significantly reduced (P<0.05). The proportion of apoptotic cells in the kidney tissues in model group were higher than that in control group (P<0.05). Compared with model group and negative transfection group, the proportion of apoptotic cells in the kidney tissues in IL-33 transfection group was significantly reduced (P<0.05). The protein expression levels of IL-1β, IL-6, TNF-α, TLR4 and MyD88 in model group were significantly higher than those in control group (P<0.05). Compared with model group and negative transfection group, the protein expression levels of IL-1β, IL-6, TNF-α, TLR4 and MyD88 in IL-33 transfection group were significantly decreased (P<0.05). CONCLUSION IL-33 gene-modified BMSCs significantly improve the renal function of AKI rats with sepsis. The mechanism may be related to IL-33 regulating TLR4/MyD88 signaling pathway and inhibiting renal inflammatory response.     

Role of IL-33/ST2 signaling pathway in fibrosis diseases

Interleukin (IL)-33 is a member of IL-1 family. It is identified as a functional ligand for ST2 which is an IL-1 receptor-like protein. IL-33/ST2 signaling is involved in T-cell-mediated immune responses. Increasing evidence indicates that IL-33 has different roles in different diseases. Recently, some studies have demonstrated that IL-33 may be related to the genesis and development of fibrosis diseases. We review current knowledge of the biological characteristics of IL-33 and the role of IL-33/ST2 signaling pathway in fibrosis diseases.     

Progress of P-selectin glycoprotein ligand-1 in kidney diseases

P-selectin glycoprotein ligand-1 (PSGL-1) is an adhesion molecule mainly expressed on the surface of leukocytes and platelets, which plays a vital part in immune recognition, inflammatory response and thrombosis. The prevalence of chronic kidney disease (CKD) is increased gradually and it has been one of major diseases that threaten the world's public health. In addition, its etiology is complicated, and most of the pathogenesis is incompletely understood. Researches show that PSGL-1 participates in the development of kidney diseases in a variety of ways, and its mechanism may involve signaling pathways such as TGF-β1/Smad and PI3K/AKT/GSK-3β, as well as key renal regulators such as connective tissue growth factor and chemokine (C-C motif) ligand 2. This review summarizes the research progress of PSGL-1 in renal fibrosis, lupus nephritis, obesity-related kidney disease and acute kidney injury.     

Clinical significance of elevated serum interleukin 15 in patients with active lupus nephritis

AIM: To detect interleukin 15 (IL-15) levels in peripheral blood from patients with active lupus nephritis and investigate its clinical significance. METHODS: IL-15 level was determined by enzyme linked immunosorbent assay (ELISA). The peripheral blood mononuclear cells (PBMCs) were isolated with grads density abaxiality. The inhibitory effects of dexamethasone on production of IL-15, IgG and anti-dsDNA antibody in cultured PBMCs from LN patients were also investigated. RESULTS: (1) Serum IL-15 level in LN patients was significantly higher than that in normal controls (P<0.01). Serum IL-15 level in active LN patients was significantly higher than that in remised patients (P<0.05). (2) Serum IL-15 level was positively correlated with SLEDAI, anti-dsDNA antibody and 24 h urine protein excretion in active LN patients. (3) Serum IL-15 level was significantly reduced in LN patients treated with combination of cyclophosphamide (CTX) and steroid for 12 weeks. (4) Secretion of IL-15, IgG and dsDNA antibody in cultured PBMCs from active LN patients was significantly higher than that in normal control group, and IL-15 level in supernatant of cultured PBMCs from active LN patients was positively correlated with IgG and dsDNA antibody. Dexamethasone inhibited the secretion of IL-15, IgG and dsDNA antibody in cultured PBMCs from LN patients. CONCLUSION: Serum IL-15 level in patients with active lupus nephritis is significantly elevated, suggesting that IL-15 may be involved in the pathophysiological process of LN. IL-15 may be used as an index to assess the activity of LN.     

Bone marrow hematopoietic microenvironment in patients with systemic lupus erythmatosus

AIM: To investigate bone marrow hematopoietic microenvironment in patients with systemic lupus erythmatosus (SLE), and to explore the pathogenesis of SLE.METHODS: Bone marrow stroma cells were collected from SLE patients.Colony forming units of stromal cells, and expression of fibronectin, laminin and type IV collagen, adhesive molecules, and some cytokines were detected by cell culture, immunohistochemistry, flow-cytometry, ELISA, and RT-PCR assay, respectively.RESULTS: The number of the colony forming units of stromal cells and their morphology in SLE group were the same as the control group (P>0.05).We did not find any difference of the expression of fibronectin, laminin and type IV collagen in them.Expression of ICAM and VCAM were (56.4±14.8)% and (55.6±12.2)%, respectively, obviously higher than those in control group (P<0.01).IL-6 in bone marrow stromal cell culture suspension of SLE was higher than that in control group (P<0.01).SCF and SDF-1 were not different between two groups (P<0.05).MIP-1 and IFN-γ in SLE patients were obviously higher than those in control group (P<0.01).TGF-β was on the opposite (P<0.01).The later three cytokines were correlated to SLEDAI score (P<0.01).CONCLUSION: Bone marrow microenvironment of SLE patients was deficient in the expression of cell surface adhesion molecules and cytokine secretion, which contributed to the pathogenesis of SLE.     

Hydrogen sulfide attenuates urosepsis-induced acute kidney injury by blocking TLR4/MyD88/PI3K signaling pathway

AIM:To explore the effect of hydrogen sulfide (H₂S) on urosepsis-induced acute kidney injury. METHODS:New Zealand white rabbits were randomly divided into control group, sham group, model (sepsis) group, NaHS treatment (NaHS) group, and NaHS combined with TAK-242 (a TLR4 inhibitor) treatment (NaHS+TAK-242) group. After treatment for 72 h, HE staining was used to measure the histopathological changes of rabbit kidney. The levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected by automatic biochemical analyzer. The serum levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), procalcitonin (PCT), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by ELISA. The TLR4/MyD88/PI3K signaling pathway-related proteins in the kidney were determined by Western blot. RESULTS:Compared with control group, obvious damage was observed in the kidneys of septic rabbits, but the kidneys were markedly improved by treatment with NaHS. The levels of BUN, SCr, NGAL, KIM-1, PCT, IL-1β, IL-6 and TNF-α in the septic rabbits were higher than those in control group, and decreased significantly in NaHS group and NaHS+TAK-242 group. The protein levels of TLR4, MyD88, p-PI3K and p-Akt in septic rabbit kidneys were higher than those in control group. However, NaHS or NaHS+TAK-242 inhibited the activation of TLR4/MyD88/PI3K signaling pathway in the kidneys of septic rabbits. CONCLUSION:H₂S play a protective effect on the rabbits with urosepsis-induced acute kidney injury by blocking TLR4/MyD88/PI3K signaling pathway to inhibit inflammatory response.     

Diagnostic value of Th17 cells in symptom severity and prognosis of chronic obstructive pulmonary disease

AIM: To observed the correlation between Th17 cell level and the symptom severity and prognostic factors of chronic obstructive pulmonary disease (COPD), and to explore the clinical application value of Th17 cell level in assessing the prognosis of patients with COPD. METHODS: The patients with diagnosed COPD (n=110) in our hospital during May 2013 to December 2014, and 40 healthy subjects were enrolled in the study. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), the COPD patients were divided into group A (low risk, less symptoms), group B (low risk, more symptoms), group C (high risk, less symptoms) and group D (high risk, more symptoms), which were given inhaled corticosteroid/long-acting β₂ agonist or corticosteroid/long-acting β₂ agonist+long-acting antimuscarinic agent treatment for 3 months. The proportion of Th17 cells, cytokines (IL-17 and IL-6), the COPD assessment test (CAT) score, age, body mass index, pulmonary function and the times of acute exacerbation of COPD in previous 1 year were observed before and after treatment. The correlation analysis between the level of Th17 cells and other clinical characteristics was performed. RESULTS: Th17 cell, IL-17 and IL-6 levels in COPD group were significantly higher than those in control group (P < 0.05). With the increase in the severity of COPD symptoms, Th17 cells, cytokines (IL-17 and IL-6) and CAT score in groups B and D were significantly higher than those in groups A and C (P < 0.05). The univariate analysis showed that the levels of Th17 cells in groups B and D before treatment were positively correlated with the CAT score (P < 0.05), which were negatively correlated with FEV₁ , FEV₁% Pred, FVC and FVC% Pred. The levels of Th17 cells were not correlated with the CAT score, FEV₁, FEV₁% Pred, FVC and FVC% Pred in groups A and C. The levels of Th17 cells after treatment were positively correlated with the CAT score, which were negatively correlated with FEV₁ , FEV₁% Pred, FVC and FVC% Pred (P < 0.05). CONCLUSION: The peripheral Th17 cell level has a good correlation with IL-17, IL-6, CAT score and pulmonary function in COPD patients, suggesting a potential value to predict the symptom severity and prognosis of COPD.     

Effects of diosmin on changes of TNF-α, IL-1β, IL-6, IL-8 and IL-10 in serum and kidney tissues of rats with kidney ischemia and reperfusion

AIM: To observe the effects of diosmin on the production of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-6, IL-8 and IL-10 in serum and kidney tissues of rats with kidney ischemia and reperfusion (I/R). METHODS: Sprague-Dawley rats (180 in total) were randomly divided into 3 groups including sham operation group (sham),I/R group and diosmin+I/R group (diosmin+I/R). At the end of the experiment, the blood and kidney tissues were obtained and TNF-α, IL-1β, IL-6, IL-8 and IL-10 were detected by ELISA. RESULTS: The levels of TNF-α, IL-1β, IL-6, IL-8 and IL-10 in serum and kidney tissues in I/R group and diosmin+I/R group were significantly higher than those in sham group (P<0.01 or P<0.05). Following the development of the pathologic process, the level of TNF-α, IL-1β, IL-6 and IL-8 was significantly increased in I/R group and diosmin+I/R groups, but the level of IL-10 was significantly decreased in I/R group and significantly increased in diosmin+I/R group. The levels of TNF-α, IL-1β, IL-6 and IL-8 in I/R group was significantly higher than those in diosmin+I/R group (except TNF-α at 1 h in diosmin+I/R group). The level of IL-10 in diosmin+I/R group was significantly higher than that in I/R group (P<0.01 or P<0.05). CONCLUSION: Diosmin not only decreases the production of TNF-α, IL-1β, IL-6 and IL-8, but also promotes the production of anti-inflammatory cytokine IL-10, suggesting that the protective effect of diosmin on kidney I/R injury was associated with anti-inflammatory mechanism.     

Effect of IL-13 on expression of IL-1β in acute renal ischemia/ reperfusion injury in rats

AIM:To investigate the effects of IL-13 on expression of IL-1β in acute renal ischemia/reperfusion injury.METHODS:Fifty-seven male Wistar rats were randomly divided into 8 group: normal group, sham operation group, ischemia group, ischemia/reperfusion injury group(I/R), normal saline(NS)-treated group 1(C-1), NS-treated group 2(C-2), IL-13-treated group1(T-1)and IL-13-treated group 2(T-2).Rats were subjected to 45 min bilateral renal ischemia followed by reperfusion. rmIL-13 (1.5 μg/50 g body weight )was injected into the renal arteries through the abdominal aorta before ischemia(T-1) or immediately afterischemia(T-2).The serum level of IL-1β and the renal expression of IL-1β were determined in each group at 24 h post-ischemia. In addition, BUN, Cr and renal histology were also measured.RESULTS:(1)The serum level of IL-1β, gene expression and protein production of IL-1β in kidney decreased markedly in IL-13-treated groups.(2)Renal function and histology were significantly improved in IL-13-treated groups, renal injury scores decreased significantly.(3)A positive correlation were found between the serum level of IL-1β and BUN, SCr(r=0.708, P＜0.01;r=0.770, P＜0.01).CONCLUSION:These data suggest that IL-13 inhibit the expression of IL-1βand improve func-tion and histology of kidney in acute renal ischemia/reperfusion injury.