Serum B7 homologous protein 2, tumor necrosis factor-related apoptosis-inducing ligand, interleukin-37, interleukin-17A levels in patients with primary immune thrombocytopenia and their clinical significance / 中国医师进修杂志

Objective:To explore the changes of serum B7 homolog 2 (B7-H2), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interleukin(IL)-37 and IL-17A levels in patients with primary immune thrombocytopenia (ITP), and to analyze the clinical guiding significance of each index level in the diagnosis and treatment of ITP.Methods:A total of 90 patients with ITP treated in Jining Hospital of Traditional Chinese Medicine from September 2018 to September 2020 were retrospectively selected as the research group, and 90 healthy patients during the same period were selected as the normal control group. The levels of serum B7-H2, TRAIL, IL-37, IL-17A and platelet count (PLT) in the two groups were compared, and the clinical guidance significance of each index level in the diagnosis and treatment of ITP were analyzed by receiver operating characteristic(ROC) curve.Results:The serum levels of B7-H2, TRAIL, IL-37 and IL-17A in the research group were higher than those in the normal control group, and PLT was lower than that in the normal control group: (25.12 ± 4.29) μg/L vs. (12.26 ± 3.10) μg/L, (0.92 ± 0.20) μg/L vs.(0.46 ± 0.13) μg/L, (145.02 ± 43.18) ng/L vs. (50.23 ± 14.07) ng/L, (21.63 ± 5.06) ng/L vs. (7.71 ± 2.04) ng/L, (16.12 ± 4.61) × 10 9/L vs. (200.86 ± 61.4) × 10 9/L, there were statistical differences ( P<0.05). After treatment for 3 months, 73 patients obtained remission, and 13 patients were non-remission. The levels of B7-H2, TRAIL, IL-37, IL-17A in the non-remission group before and after treatment were higher than those in the remission group, and PLT was lower than that in the remission group, there were statistical differences ( P<0.05). Pearson correlation analysis showed that the levels of serum B7-H2, TRAIL, IL-37 and IL-17A were negatively correlated with PLT ( P<0.05). The ROC curve analysis showed that the area under the curve of serum B7-H2, TRAIL, IL-37 and IL-17A in prognostic prediction was 0.916, the sensitivity and the specificity were 94.12% and 86.30%. Conclusions:The serum levels of B7-H2, TRAIL, IL-37 and IL-17A in patients with ITP are significantly elevated, and are closely related to the level of PLT. Combined detection can help clinically predict the direction of disease outcome.

Expression of interleukin-17A in serum of children with intravenous immunoglobulin-resistant Kawasaki disease and its clinical significance / 中国当代儿科杂志

OBJECTIVES@#To study the expression of interleukin-17A (IL-17A) in the serum of children with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) and its clinical significance.@*METHODS@#A total of 143 children with KD who were hospitalized in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from June 2021 to June 2022 were enrolled in this prospective study, among whom 115 had IVIG-sensitive KD and 28 had IVIG-resistant KD. After matching for sex and age, 110 children with acute respiratory infectious diseases (fever time ≥5 days but without KD) were enrolled as the control group. The enzyme-linked immunosorbent assay was used to measure the serum level of IL-17A. The levels of white blood cell count (WBC), neutrophil count (NE), platelet count, erythrocyte sedimentation rate, and C-reactive protein (CRP) were measured. The receiver operating characteristic curve was plotted to analyze the value of WBC, NE, CRP, and IL-17A in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis was used to evaluate the predictive factors for resistance to IVIG in children with KD.@*RESULTS@#Before IVIG treatment, the KD group had a significantly higher serum level of IL-17A than the control group (P<0.05), and the children with IVIG-resistant KD had a significantly higher serum level of IL-17A than those with IVIG-sensitive KD (P<0.05). The receiver operating characteristic curve analysis showed that WBC, NE, CRP, and IL-17A had an area under the curve of 0.718, 0.741, 0.627, and 0.840, respectively, in the prediction of IVIG-resistant KD. With serum IL-17A ≥44.06 pg/mL as the cut-off value, IL-17A had a sensitivity of 84% and a specificity of 81% in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis showed that a high serum level of IL-17A was a predictive factor for resistance to IVIG in children with KD (OR=1.161, P=0.001).@*CONCLUSIONS@#Serum IL-17A levels are elevated in children with IVIG-resistant KD, and serum IL-17A level (≥44.06 pg/mL) may have a predictive value for resistance to IVIG in children with KD.

Interleukin-17A in Egyptian leprosy patients: a clinical, genetic, and biochemical study

Abstract Background: Leprosy represents a long-term communicable disease resulting from Mycobacterium leprae infection. IL-17A is one of the pro-inflammatory cytokines that protects humans against many fungal and bacterial pathogens. Objective: To investigate IL-17A (rs2275913) gene polymorphism and its circulating level in leprosy patients, and to correlate the detected results with different clinical aspects of leprosy in the investigated patients. Methods: 60 patients with leprosy, and 29 age and sex-matched volunteers were investigated for IL-17A serum level and IL-17A single nucleotide polymorphism (SNP) by ELISA and RFLP-PCR respectively. Results: IL-17A serum level was significantly higher in leprosy patients than in controls (p = 0.034), and in TL than LL (p = 0.017). IL-17A (rs2275913 A/G) G allele and GG genotype were associated significantly with LL (p = 0.005and 0.001 respectively). IL-17A (rs2275913 A/G) AG genotype carriers demonstrated the highest IL-17A serum levels; however, its lowest levels were found in IL-17A (rs2275913 A/G) AA genotype carriers (p = 0.005). Grade 2 disability (p = 0.030) and positive slit skin smear (SSS) (p = 0.005) were significantly associated with IL-17A (rs2275913 A/G) GG genotype. Study limitations: The small number of studied subjects. Conclusions: IL -17A may have a pivotal role in leprosy pathogenesis. IL-17A (rs2275913) GG genotype plus G allele might be related to the development of LL in the Egyptian population.

Interleukin-17A-mediated psoriasis and cardiovascular comorbidities / 中华皮肤科杂志

The interleukin (IL) -23/IL-17 axis is the main pathway in the pathogenesis of plaque-type psoriasis vulgaris, and IL-17A plays a key role in the relevant immune pathways. IL-17A mediates overlapping inflammatory pathways in atherosclerosis and psoriasis, promotes inflammation, coagulation and thrombosis, and plays an important role in the occurrence and development of cardiovascular comorbidities in patients with psoriasis. Inhibiting the inflammatory effect of IL-17A can reduce the incidence and mortality of cardiovascular comorbidities in patients with severe psoriasis. This review summarizes recent research progress in IL-17A-mediated systemic inflammation and cardiovascular comorbidities in patients with psoriasis, and provides a reference for prevention and reduction of cardiovascular comorbidities in patients with psoriasis in clinical practice.

Interleukin-17A is closely correlated with the progression of renal epithelial-mesenchymal transition in spontaneously hypertensive rats / 南方医科大学学报

OBJECTIVE@#To explore the role of interleukin-17A (IL-17A) in renal epithelial- mesenchymal transition (EMT) in essential hypertensive nephropathy.@*METHODS@#Four-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (control group) were both randomized into 4 groups (n=5) for observation at 4, 6, 10 and 30 weeks of age. Blood pressure of the rats was monitored using a noninvasive tail artery blood pressure measurement instrument. The percentage of Th17 cells in the splenocytes was analyzed using flow cytometry. The mRNA and protein expression levels of IL-17A, iNOS, Arg-1, E-cadherin, and α-SMA in the kidneys of the rats were detected using RT-PCR and immunohistochemical staining, respectively, and plasma levels of IL-17A were regularly detected using ELISA.@*RESULTS@#At the age of 6 weeks, the SHRs began to show significantly higher blood pressure with greater Th17 cell percentage in the splenocytes and high renal expression and plasma level of IL-17A than WKY rats (P < 0.05 or P < 0.01). At 30 weeks, renal expression of E-cadherin mRNA and protein was significantly lower and the expression of Arg-1 mRNA and protein was significantly higher in SHR than in WKY rats (P < 0.01). Compared with the WKY rats, the SHRs showed significantly higher mRNA and protein expressions of iNOS at 6 and 10 weeks (P < 0.05 or 0.01) and higher α-SMA mRNA and protein expressions since 10 weeks of age (P < 0.05 or 0.01). In SHRs older than 10 weeks, renal IL-17A mRNA and protein expression levels were negatively correlated with those of E-cadherin (r=-0.731, P < 0.05; r=-0.827, P < 0.01) and positively correlated with those of α-SMA (r=0.658, P < 0.05; r=0.968, P < 0.01).@*CONCLUSION@#IL-17A is closely correlated with the progression of renal EMT in SHR and plays its role possibly by mediating M1/M2 polarization of renal infiltrating macrophages.

Tumor necrosis factor α-mediated low expression of fatty acid desaturase 2 in psoriasis / 中华皮肤科杂志

Objective:To investigate the expression of fatty acid desaturase 2 (FADS2) in psoriatic skin lesions, as well as its regulatory factors.Methods:FADS2 expression in psoriatic skin lesions was analyzed by using the dataset GDS4602 in Gene Expression Omnibus (GEO) database. Skin tissues were obtained from the back of 5 C57BL/6 mouse models of imiquimod-induced psoriasis, normal skin of 4 patients without psoriasis or other immune skin diseases, lesions of 4 patients with psoriasis before and after 10-week treatment with infliximab, as well as lesions of 3 patients with psoriasis before and after 12-week treatment with secukinumab in Shanghai Skin Disease Hospital. FADS2 expression was determined by both immunohistochemical staining and Western blot analysis in the epidermis of mouse skin tissues, and by immunohistochemical staining in that of human skin tissues. In vitro cultured human immortalized keratinocytes (HaCaT) were divided into several groups to be treated with 50 ng/ml tumor necrosis factor-α (TNF-α) alone for 0, 6, 12 and 24 hours respectively, 200 ng/ml interleukin-17A (IL-17A) alone for 0, 6 and 12 hours respectively, or treated with 50 ng/ml TNF-α and 5 μmol/L BAY 11-7082 (a nuclear factor-κB pathway inhibitor) for 6 hours (TNF-α+ BAY 11-7082 6 h group) , and the cells receiving normal culture served as the control group. After the above treatment, real-time fluorescence-based quantitative PCR (qPCR) and Western blot analysis were conducted to determine the mRNA and protein expression of FADS2 respectively. Statistical analysis was carried out by using one-way analysis of variance and t test. Results:Analysis of the dataset GDS4602 showed that the FADS2 mRNA expression was significantly lower in the lesional and non-lesional skin tissues from the patients with psoriasis (0.656 ± 0.475, 1.503 ± 1.062, respectively) than in the normal skin tissues (2.035 ± 1.226; F = 55.17, 3.07, P < 0.001, = 0.012, respectively) , and was significantly lower in the lesional skin tissues than in the non-lesional skin tissues from the patients with psoriasis ( F = 26.27, P < 0.001) . Western blot analysis and immunohistochemical staining both showed significantly decreased FADS2 protein expression in the mouse skin tissues in the imiquimod group (gray-value ratio: 0.463 ± 0.172; fluorescence intensity: 21.840 ± 3.125) compared with the normal control group (gray-value ratio: 1.000, t = 7.00, P = 0.002; fluorescence intensity: 30.720 ± 6.850, t = 3.15, P = 0.035) . Compared with the skin lesions before treatment, the FADS2 protein expression significantly increased in the skin lesions from the patients with psoriasis after 10-week treatment with infliximab (43.775± 3.342 vs. 27.950 ±1.218, t = -6.95, P = 0.006) , but was not significantly changed in the skin lesions from the patients with psoriasis after 12-week treatment with secukinumab (28.667 ± 3.402 vs. 31.933 ± 2.987, t = 2.72, P = 0.113) . qPCR revealed that the FADS2 mRNA expression significantly decreased in HaCaT cells in the TNF-α 6 h group and TNF-α 12 h group compared with the TNF-α 0 h group ( P = 0.002, 0.003, respectively) , while there was no significant change in the FADS2 mRNA expression in the IL-17A 6 h group and IL-17A 12 h group compared with the IL-17A 0 h group ( P = 0.849, 0.961, respectively) . The FADS2 mRNA expression significantly decreased in HaCaT cells in the TNF-α 6 h group (0.682 ± 0.132) compared with the control group (1.000, t = 4.82, P = 0.017) , but significantly increased in the TNF-α + BAY 11-7082 6 h group (1.541 ± 0.525) compared with the TNF-α 6 h group ( t = -3.58, P = 0.037) . Western blot analysis revealed significantly decreased FADS2 protein expression in HaCaT cells in the TNF-α 24 h group compared with the TNF-α 0 h group ( F = 6.24, P = 0.013) . Conclusion:FADS2 expression was downregulated in psoriatic lesions, which may be related to TNF-α.

Polydatin Ameliorated Colonic Inflammation via Precluding Phosphorylation of PKCθ/STAT3 Pathway to Inhibit Th17 Cells in Mice with Ulcerative Colitis / 中国实验方剂学杂志

Objective:To investigate the therapeutic effect of polydatin on ulcerative colitis （UC） in mice and its regulation of protein kinase C<italic>θ</italic>（PKC<italic>θ</italic>）/signal transducer and activator of transcription 3（STAT3） signaling on T helper cell 17（Th17） and its mechanism in the treatment of UC. Method:The 32 male C57BL/6 mice were randomly divided into normal group， model group， polydatin group （0.045 g·kg^-1） and sulfasalazine group （0.5 g·kg^-1）. The UC model was established by giving 3% dextran sodium sulfate （DSS） solution to free drinking water in mice. Polydatin and sulfasalazine groups were given by gavage 0.5 h before modeling for 7 days. The normal group and model group were given the same amount of normal saline. After the last administration， the colonic tissue was taken and hematoxylin-eosin （HE） was used to observe the pathological changes of colonic tissue. Flow cytometry was used to detect the proportion of Th17 in the lamina propria of colonic mucosa. The expression of interleukin-17A （IL-17A） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Polydatin was added to CD4⁺T cells purified from spleen of C57BL/6 mice by magnetic-activated cell sorting （MACS） under the stimulation of cell stimulation cocktail <italic>in vitro </italic>in order to detect its impact on PKC<italic>θ</italic> and STAT3 phosphorylation. Result:Compared with normal group， the body weight was significantly decreased， and disease activity index （DAI） scores of the model group was significantly increased （<italic>P</italic><0.01）， the colonic mucosal epithelium was damaged and inflammatory cells infiltration in the mucosa and submucosa was obvious， the proportion of Th17 in the lamina propria of colonic mucosa was significantly increased （<italic>P</italic><0.01）， and the content of serum IL-17A was significantly increased （<italic>P</italic><0.01）. Compared with the model group， the weight and DAI score of polydatin and sulfasalazine groups were significantly improved （<italic>P</italic><0.01）， the degree of colon tissue damage was significantly improved， the proportion of Th17 in colon mucosa lamina propria was significantly decreased （<italic>P</italic><0.01）， and the content of IL-17A in serum was significantly decreased （<italic>P</italic><0.01）. <italic>In vitro</italic> experiments showed that polydatin could significantly inhibit the phosphorylation of PKC<italic>θ</italic> and STAT3 in Th17 （<italic>P</italic><0.01） as well as IL-17A secretion. Conclusion:Polydatin can improve the ulcerative colitis in mice via inhibiting the phosphorylation of PKC<italic>θ</italic> and STAT3 to preclude IL-17A secreting in Th17.

Modulation of Wnt/ß-catenin signaling in IL-17A-mediated macrophage polarization of RAW264. 7 cells

Macrophages play pivotal roles in host defense and immune homeostasis, which have two major functional polarization states, the classically activated M1 and the alternatively activated M2. Interleukin (IL)-17A is an immune modulator able to shape macrophage phenotypes. Wnt/β-catenin is a developmental signaling pathway that plays crucial roles in morphogenesis and tissue homeostasis, which has also been recently demonstrated playing roles in immune regulation. A growing amount of evidence suggests that both Wnt and IL-17A signaling are involved in macrophage polarization. However, their interaction in macrophage polarization remains elusive. The aim of present study was to explore impacts of Wnt/β-catenin on IL-17A-mediated macrophage M1/M2 polarization in murine monocyte/macrophage-like cell line RAW264.7. Results revealed that IL-17A activated Wnt/β-catenin signaling and induced macrophage M1 polarization, but inhibited M2 polarization. In contrast, the activation of Wnt/β-catenin signaling led to the inhibition of M1 macrophage polarization but the promotion of M2 polarization. Importantly, the activation of Wnt/β-catenin also showed abilities to inhibit the IL-17A-induced M1 macrophage polarization while diminishing the IL-17A-inhibited M2 polarization. Molecular analysis further uncovered that the JAK/STAT signaling pathway was involved in the interaction of Wnt/β-catenin and IL-17A in the modulation of macrophage polarization. These results suggested that the Wnt/β-catenin signaling modulated IL-17A-altered macrophage polarization in part by regulating the JAK/STAT signaling pathway. This study thus revealed a novel function of Wnt/β-catenin signaling in regulating IL-17A-altered macrophage polarization.

IL-17A/lL-17RA reduces cisplatin sensitivity of ovarian cancer SKOV3 cells by regulating autophagy / 南方医科大学学报

OBJECTIVE@#To investigate the effect of interleukin-17A (IL-17A) on chemosensitivity of ovarian cancer cells to cisplatin (DDP) and explore the mechanism in light of autophagy regulation.@*METHODS@#Ovarian cancer SKOV3 cells cultured @*RESULTS@#DDP increased the expression of IL-17RA in ovarian cancer SKOV3 cells. Treatment with IL-17A significantly reduced the susceptibility of SKOV3 cells to cisplatin-induced apoptosis (@*CONCLUSIONS@#IL-17A/IL-17RA can decrease chemosensitivity of SKOV3 cells to DDP by upregulating DDP-induced autophagy.

IL-17A activates mouse lung fibroblasts through promoting chemokine CXCL12 secretion / 浙江大学学报·医学版

OBJECTIVE@#To investigate the role of IL-17A in promoting the activation of lung fibroblasts and the secretion of chemokine CXCL12, and to explore the possible mechanism.@*METHODS@#Lung tissues of BALB/c mice were collected after intraperitoneal injection of recombinant mouse IL-17A (rmIL-17A). Real-time RT-PCR and Western blotting were used to detect the expression levels of α-smooth muscle actin (α-SMA) and collagen I in lung tissues, and immunohistochemical staining and real-time RT-PCR were used to determine the expression of CXCL12. Normal mouse primary lung fibroblasts were isolated and cultured, and identified by immunofluorescence staining with optical microscopy. Cells and supernatant of culture medium were collected after stimulation with rmIL-17A at different concentrations. mRNA levels of α-SMA, collagen I, and CXCL12 in the cells were determined by real-time RT-PCR, and the levels of collagen I and CXCL12 in the supernatant of culture medium were determined by ELISA.@*RESULTS@#The mRNA and protein levels of α-SMA and collagen I in the lung tissue of mice injected with rmIL-17A were significantly increased compared with the control group (all @*CONCLUSIONS@#s: IL-17A can promote the activation of lung fibroblasts and translation into myofibroblast. The secretion of collagen is increased, which promote the deposition of extracullular matrix, and leads to the occurrence and development of lung fibrosis. CXCL12, a chemokine secreted by activated fibroblasts, may be involved in this process.

Role of Salivary Immune Parameters in Patients With Primary Sjögren's Syndrome

BACKGROUND: Several factors, including clinical manifestations and laboratory data, have been used to evaluate the disease activity of Sjögren's syndrome (SS). We investigated saliva indicators of disease activity in primary SS patients. METHODS: We enrolled 138 Taiwanese patients with primary SS and 100 Taiwanese normal controls. Interleukin (IL)-6, IL-17A, tumor necrosis factor-alpha (TNF-α), and rheumatoid factor (RF)-IgA levels in saliva samples were measured using ELISA or fluorescent enzyme-linked immunoassay. Serum IgG, IgA, and IgM levels were measured by nephelometry. Erythrocyte sedimentation rate (ESR) was measured with an automatic ESR analyzer. The t-test and Pearson correlation test were used. RESULTS: IL-6 level was higher in primary SS patients than in normal controls (14.23±14.77 vs 9.87±7.32, P=0.012), but there were no significant differences in IL-17A, TNF-α, and RF-IgA levels. In primary SS patients, IL-6 level correlated weakly with ESR and IgG levels (r=0.252, P=0.015, and r=0.248, P=0.017, respectively), and TNF-α level correlated weakly with IgG level (r=0.231, P=0.024). CONCLUSIONS: IL-6 may play a role in SS pathogenesis. Saliva IL-6 might be an indicator of disease activity in primary SS patients.

Effect of recombinant human IL-17A on growth of colon cancer cells and its mechanism / 吉林大学学报(医学版)

Objective: To explore the effect of recombinant human interleukin-17AI (IL-17A) on the growth of colon cancer cells, and to investigate the related mechanism. Methods: The colon cancer SW480 cells were divided into control group and experimental group. The SW480 cells in control group were untreated and the SW480 cells in experimental group were added with 50 fig • L_1IL-17A. The proliferation abilities of SW480 cells in two groups were detected by CKK-8 method. The levels of IL-17A in the SW480 cells in two groups were detected by ELISA, and the expression levels of signal transducers and activators of transcription 3 (STAT3) and p-signal transducers and activators of transcriptions 3 (p-STAT3) were examined by Western blotting methed. Results: Compared with control group, the proliferation ability of the SW480 cells in experimental group was increased (P < 0 . 05). The level of IL-17A in the SW480 cells in experimental group was significantly higher than that in control group (P< 0. 01). Compared with control group, the expression levels of STAT3 and p-STAT3 proteins in the SW480 cells in experimental group were significantly higher than those in control group (P < 0 . 01). Conclusion: Recombinant protein IL-17A can stimulate the growth of colon cancer SW480 cells, which may be related to the activation of STAT3 signaling pathway.

IL-17A inhibits degradation of ABCA1 protein through p38MAPK in macrophages / 西安交通大学学报(医学版)

Objective: To investigate the underlying mechanisms and intracellular signaling of up-regulating adenosine triphosphate binding cassette transporter A1 (ABCA1) by interleukin-17A (IL-17) in macrophages. Methods: Mouse RAW264.7 cells were treated with 20ng/mL of IL-17A. The protein expressions of ABCA1 and p-p38MAPK were detected using Western blot. The ubiquitination level of ABCA1 was detected using Co-immunoprecipitation. Results: IL-17A increased the expression of ABCA1 at the protein level, but not at the mRNA level. IL-17A reduced the degradation of ABCA1 protein. IL-17A attenuated binding of ABCA1 to ubiquitin. SB203580, p38MAPK inhibitor, reversed the decrease of ubiquitination and increased expression of ABCA1 protein induced by IL-17A in macrophages. Conclusion: IL-17A increases the expression of ABCA1 protein by inhibiting its degradation through p38MAPK pathway in macrophages.

A Case of Rapid Progressive Neurosyphilis in Patient with Ankylosing Spondylitis Who Is Treating Anti-interleukin 17A Monoclonal Antibody, Secukinumab

Anti-interleukin 17A agent, secukinumab is remarkably effective for treating patients with ankylosing spondylitis. However, the main safety concern of secukinumab is an increased risk of infection. Generally, neurosyphilis occurs a few years after the primary syphilitic infection. Rare cases of progressing to neurosyphilis with a much lower latency were reported. We report a case of rapid progressive neurosyphilis involving hearing loss in both ears in a patient with ankylosing spondylitis who was treated with secukinumab.

Changes of autophagy in rat lung tissue after acute spinal cord injury / 中华创伤杂志

Objective To investigate the changes of autophagy in rat lung tissues after acute spinal cord injury (ASCI) and the possible mechanisms.Methods Sixty-three female SD rats were divided into sham operation group (n =21) and spinal cord injury group (n =42),according to the random number table.The modified Allen method with the impact energy of 10 × 25 g · mm at the T10 vertebra was used for preparation of ASCI models.The rats were sacrificed at 6,12,24,48,72 hours,1 and 2 weeks after injury.Lung tissue damage and apoptosis were detected by HE staining and TUNEL method.The changes of autophagy and expressions of LC3-Ⅱ,P62,Beclin-1,interleukin (IL)-17A and Bcl-2 in lung were detected by Western blot and immunofluorescence.Results The pulmonary alveoli maintained normal structure in sham operation group,with no inflammation or pulmonary hemorrhage.Slight lung tissue damages were observed in spinal cord injury group at 12 h postinjury.Alveolar stroma widening,inflammatory infiltration,hemorrhage,and alveolar collapse became ingravescent at 24-72 hours postinjury.Numbers of apoptotic cells in spinal cord injury group were 551.22 ± 135.94,905.11 ±92.64,and 141.78 ± 30.86 respectively at 24,72 hours and 1 week postinjury,and were significantly increased at 24 and 72 hours postinjury,compared with sham operation group (P ＜ 0.05).Expression of LC3-II in spinal cord injury group was increased at 24-72 hours postinjury,compared with sham operation group (P ＜ 0.05).Expression of P62 in spinal cord injury group was up regulated at 24-72 hours postinjury,compared with sham operation group (P ＜ 0.05).Expression of Beclin-1 in spinal cord injury group was increased at 24 h postinjury and then dropped at 48-72 hours,compared with sham operation group (P ＜ 0.05).Expression of IL-17A in spinal cord injury group was increased at 24-48 hours,compared with sham operation group (P ＜ 0.05).Expression of Bcl-2 in spinal cord injury group was increased from 24 hours to 72 hours,compared with sham operation group (P ＜ 0.05).Conclusion Autophagosome formation is increased and accumulated in the lung tissues after ASCI,which might be related to the increased interaction between Beclin-1 and Bcl-2 because of the up regulation of Bcl-2 by IL 17A,ultimately leading to the inhibition of autophagy.

Detection and Analysis of Candida Albicans Enolase Antigen-Specific T Cells in Heathy Individuals by ELISPOT Assay / 现代检验医学杂志

Objective To observe the T cells immune response to Enolase (Eno),an immunodominant antigen of Candida albicans.Methods Determined the frequencies of positive spot-forming cells (SFCs) of Eno antigen-specific T cells secreting IFN-γ,IL-4 and IL-17A in the PBMCs of 25 healthy individuals by ELISPOT assay.Results After Eno stimulation,the SFCs of IFN-γ,IL-4 and IL 17A in 25 healthy persons were 14.00(8.50,39.00),0(0,0) and 2(1,4.50),respectively.Either the SFCs of IFN-γ or those of IL-17A were significantly higher than those of IL-4 (P＜0.05).The difference between SFCs of IFN-γ and those of IL-17A was also significant (P=0).The response rates of IFN-γ,IL-4 and IL-17A were 100％ (25/25),4.00％ (1/25) and 88.00％ (22/25),respectively.The difference between either IFN-γor IL 17A and IL-4 was significant (values all P＜0.05).Eno induced strong response (SCFs≥20) for IFN-γ in 10 healthy individuals (40.00％,10/25),but failed to induce strong response for IL-17A and IL-4 in all the volunteers.Major healthy individuals (84.00％,21/25)showed both Th1 and Th17 cells response against Eno,12.00％ (3/25) showing Th1 cells response in isolation,and none showed Th2 or Th17 cells response individually.Conclusion Eno of Candida albicans could induce immunodominant responses of Th1 and Th17 cells,which was considered to provide protection to IC.Eno might be a potential protective vaccine against IC.

Association of IL-17 A gene promoter polymorphism with blood lipid and inflammatory factors in patients with coronary heart disease / 重庆医学

Objective To investigate the association between interleukin-17 A (IL-17 A) gene promoter polymorphism and blood lipid and inflammatory factors in coronary heart disease.Methods A total of 241 patients with coronary heart disease who were admitted to hospital from April 2010 to December 2016 were enrolled in this study.68 cases of healthy subjects were collected.IL-17 gene promoter rs8193036 genotype,blood lipid and inflammatory factors were detected and compared.Results Compared with the control group,the genotype CC,CT and TT of the rs8193036 genotype in the coronary heart disease group were significantly different (P＜0.05),and the frequency of C allele in the coronary heart disease group was significantly higher than that in the control group (P＜0.05).The levels of triglyceride,low-density lipoproteinCholesterol,high density lipoprotein cholesterol,interleukin-17a,interleukin-6,interleukin-8 and tumor necrosis factor alpha in CC genotype of tumor necrosis factor alpha group were significantly higher than those in tumor necrosis factor alpha group (P＜0.05),high density lipoprotein cholesterol decreased significantly (P＜0.05).Total cholesterol and low-density lipoprotein cholesterol had no significant differences (P ＞ 0.05).Conclusion The rs8193036 polymorphism of IL-17A gene promoter is associated with the pathogenesis of coronary heart disease.The C allele is an important genetic marker of coronary heart disease.The polymorphism of IL-17A promoter rs8193036 might affect coronary heart disease by increasing blood lipids and inflammation factors.

The inhibition of interleukin-25 on the effect of interleukin-17 for ERK1/2 and matrix metalloprotei-3 in rheumatoid arthritis fibroblast-like synoviocytes / 中华风湿病学杂志

Objective To study the function of interleukin (IL)-25 for rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) differentiation as well as on the expression of extracellular regulating protein kinase (ERK) and matrix metalloproteinases-3 (MMP-3).Methods The differences on ERK1/2 and MMP-3 protein levels were tested in RA-FLS of RA patients and healthy controls,then IL-17A (10 ng/ml) was tested when the RA-FLS were co-stimulated with different concentrations of IL-25 (0.01,0.1,1 and 10 ng/ml) and IL-17A(10 ng/ml) for 24 hours respectively.The expression of ERK1/2 and MMP-3 protein was detected by the Western blot.T test was used for the comparison between different groups.Results The expression of ERK1/2 (1.71±0.17) and MMP-3 (0.50±0.13) proteins in RA-FLS was higher than the healthy controls (0.50±0.15,0.17±0.05) (t=-9.13,P＜0.01 and t=-4.10,P＜0.05),after stimulated with IL-17A,the expression of ERK1/2 (0.77±0.22) and MMP-3 (0.59±0.13) proteins in RA-FLS were increased compared with the untreated groups (0.18±0.35,0.04±0.03) (t=-4.69,P＜0.01 and t=-7.47,P＜0.01).With increase of the concentration on IL-25,the level of ERK1/2 (0.54±0.26,0.48±0.18,0.48±0.23,0.23±0.06) and MMP-3 (0.58±0.09,0.59±0.14,0.21±0.04,0.04±0.02) in RA-FLS which were stimulated by IL-17A was decreased slowly (t=4.22,P＜0.05 and t=4.95,P＜0.01 and t=7.47,P＜0.01).Conclusion IL-25 can inhibit the stimulation of IL-17A on ERK1/2 and MMP-3 fractionally,which implies that it may take part in the development of RA through this pathway and may be a target for the RA treatment.

Detection of Candida albicans fructose bisphosphate aldolase antigen-specific T cells in healthy individuals by ELISPOT assay / 医学研究生学报

Objective Invasive candidiasis is associated with a significant mortality clinically.The purpose of this study was to observe the T cells immune response to fructose bisphosphate aldolase (Fba), an immunodominant antigen of Candida albicans, and determine whether the antigen has the possibility of priming cellular immune protection in invasive candiasis.Methods Using ELISPOT assay, we determined the frequencies of positive spot-forming cells (SFCs) of Fba antigen-specific T cells secreting IFN-γ, IL-4 and IL-17A in the peripheral blood mononuclear cells (PBMCs) of 26 healthy individuals.Results After Fba stimulation, the frequencies of positive SFCs of IFN-γ, IL-4 and IL-17A in the 26 healthy subjects were 23 (9.75, 42.50), 0 (0, 0.25) and 1.5 (0.75, 8.25), respectively, with statistically significant differences among the three (P<0.01).The response rates of IFN-γ (100% [26/26]) and IL-17A (76.92% [20/26]) were significantly higher than that of IL-4 (15.38% [4/26]) (P<0.01).Fba-induced strong response (SCFs ≥20) for IFN-γ was observed in 57.69% (15/26) of the healthy individuals, that for IL-17A in only 1, while that for IL-4 in none.Responses of both Th1 and Th17 cells to Fba were found in 65.38% (17/26) of the subjects, that of Th1 cells in 19.23% (5/26), but that of Th2 cells in none.Conclusion Fba of Candida albicans can induce immunodominant responses of Th1 and Th17 cells and is a potential vaccine against invasive candiasis.

Effects of Interleukin?17A on Acute Paraquat?intoxication?induced Kidney Injury in Mice / 中国医科大学学报

Objective To investigate the effects of interleukin?17A on kidney injury induced by paraquat(PQ). Methods Seventy?two ICR mice were randomly divided into 3 groups:NS,PQ,and PQ+Ab (n=24 for each). The PQ?poisoning model was established by administering a gavage of PQ solution;mice in the PQ+Ab group were then administereda dose of anti?IL?17A antibody 2 hours later by i.p. injection,whereas the NS group were administered a corresponding volume of normal saline instead.The mice were killed at 8,24,48,or 72 h to obtain renal tissues and serum. An enzyme?linked immunosorbent assay(ELISA)was used to determine serum IL?17A,serum creatinine(SCr),and blood urea nitrogen (BUN)levels.Chemical colorimetry was used to detect the viability of myeloperoxidase(MPO )in renal tissue,and hematoxylin?eosin(HE)stain?ing was used to observe the renal pathologic changes. Immunohistochemistry(IHC)and PCR were used to examine IL?17A expression in renal tis?sues. Results Serum IL?17A,renal tissue MPO viabilities,BUN,and SCr were increased in the PQ and PQ+Ab groups,compared to those in the NS group(P<0.01). However,the above?mentioned parameters were lower in the PQ+Ab group than in the PQ group(P<0.01). Conclusion IL?17A promotes mouse kidney injury induced by acute PQ?intoxication through activating and/or recruiting neutrophils;therefore,blockade IL?17A,with antibody can attenuate the injury.