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Growth stimulating gene 2 (ST2) protein is a member of the interleukin-1 receptor family. It is mainly divided into a soluble secreted form sST2 and a transmembrane form ST2L. sST2 is a decoy receptor that competitively binds to interleukin-33 to block the interleukin-33/ST2L signaling pathway, worsening myocardial hypertrophy, fibrosis, and ventricular dysfunction. Measuring sST2 is of important value for diagnosis and/or prognosis evaluation of cardiovascular diseases. This paper mainly reviews the research progress in the relationship between cardiovascular diseases such as heart failure, coronary heart disease, hypertension, atrial fibrillation, myocarditis, cardiomyopathy, acute aortic dissection, and pulmonary hypertension, and sST2.
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Interleukin-33 (IL-33),a novel member of IL-1 family,is a multifunctional cytokine.IL-33 can act as a transcriptional repressor.It can also bind to growth stimulation expressed gene 2 protein (ST2) to induce the activation of some inflammatory cells.IL-33 is extensively expressed in nervous system.Some studies showed that the levels of IL-33 and ST2 were significantly changed in pain.Some reports demonstrated that the IL-33/ST2 signaling pathway played critical roles in them.This present article will review the biological characteristics of IL-33/ST2 and their expressions in nervous system and significance of interventional pain related diseases.
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Objective To investigate the correlation between interleukin-1β(IL-1β),interleukin-1 receptor antagonist(IL-1 ra)and the obesity of polycystic ovary syndrome(PCOS).Methods(1)From Oct.2006 to Jan.2007,118 PCOS patients were enrolled in this study in Peking University Third Hospital,which were divided into 56 patients in obese PCOS group and 62 patients in non-obese PCOS group according to the WHO International Obesity Task Force Asia-Pacific criteria[body mass index(BMI)25 kg/m2].The polymorphism of IL-1β gene promoter region,exon-5 and intron 2 of IL-1 ra gene were detected by PCR.(2)Twenty-nine obese PCOS patients and 31 non-obese PCOS patients were selected randomizedly serum levels of IL-1β,IL-1 ra were measured by ELISA,in the mean time,serum levels of fasting glucose,fasting insulin and the total white blood cell,hypersensitive C-reactive protein levels were measured.Results(1)Genetic test:the frequency of TT genotype and T allele of IL-1β promoter region(-511)in obese PCOS patients were significantly higher than those in non-obese patients(44.6％ vs.11.3％,63.4％ vs.39.5％,all P ＜0.05).The frequency of IL-1 ra Ⅰ / Ⅴ genotype and Ⅴ allele of IL-1 ra gene were 19.6％ and 9.8％ in obese PCOS patients,which were significantly higher than those in non-obese group(3.2％ and 1.6％,P ＜0.05).(2)Serological test:serum level of IL-1β and IL-1ra of(149 ±36)and(284 ±97)ng/L in obese PCOS group which were significantly higher than those in non-obese PCOS group[(96 ± 42)and(208 ± 84)ng/L,P ＜ 0.05].Fasting blood glucose,fasting insulin and hypersensitive C-reactive protein and white blood cell count were(5.1 ± 0.7)mmol/L,(17 ± 9)mU/L,(1.5 ± 0.6)mg/L and(7.0 ± 2.3)× 109/L in obese PCOS group,which were significantly higher than in non-obese PCOS group[(4.9 ±0.5)mmol/L,(11 ±8)mU/L,(0.9 ±0.4)mg/L and(5.9 ±1.3)× 109/L,P＜0.05].(3)The correlation between interleukin and BMI: serum levels of IL-1β(r =0.673)and IL-1 ra(r =0.557)were positively correlated with BMI in PCOS patients(P ＜ 0.05).Conclusions Inflammatory factors IL-1β and IL-1ra had correlation with obesity of PCOS patients,PCOS patients who carried T allele of IL-1β gene promoter region(-511)and Ⅴ allele of IL-1ra gene were high risk of obesity.
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Objective To investigate the characteristic and its clinical value of tumor necrosis factor (TNF)-α and its receptor, interleukin (IL)-1β and its receptor in serum and bronchoalveolar lavage fluid(BALF) in patients with pulmonary tuberculosis and to determine the role of them in the immunopathogenesis of tuberculosis. Methods The concentrations of TNF-α,soluble TNF receptor (sTNF-R) Ⅰ, IL-1β and IL-1 receptor were measured using sandwish ABC-enzyme-linked immunosorbent assay (ELISA) method in serum and BALF of 46 patients with active tuberculosis and 21 patients with inactive tuberculosis, and in the serum of 20 cases of healthy control. Meanwhile the above-mentioned cytokine levels in serum and BALF of 19 patients with active tuberculosis were followed up. Differences between groups were assessed for significance by t test. Results The TNF-α,sTNF-R Ⅰ, IL-1β and IL-1 receptor levels and TNF-α/sTNF-R Ⅰ ratios in BALF of active tuberculosis group were (286.2±96.3) pg/L,(2 431.5±1 124.6) pg/L,(58.6±3.2) pg/L,(162.4±17.1) pg/L and 0.06±0.01, respectively, which were all significantly higher than those with inactive tuberculosis group (t=3.36,3.25,2.95,2.27 and 3.12 respectively; P<0.05). The TNF-α,sTNF-R Ⅰ,IL-1β and IL-1 receptor levels and TNF-α/sTNF-R Ⅰ ratios in BALF of cavernous tuberculosis group were (381.4±106.4) pg/L,(2 824.7±1 318.5) pg/L,(66.4±4.6) pg/L,(176.4±18.7) pg/L and 0.07±0.01, respectively,which were all significantly higher than those of non-cavernous tuberculosis group (t= 3.46,2.37, 3.19, 2.99 and 3.22, respectively; P<0.05). After 2-month' antituberculosis treatments, among 19 cases, the TNF-α,sTNF-R Ⅰ,IL-1β and IL-1 receptor levels and TNF-α/sTNF-R Ⅰ ratios in BALF of 16 cases were significantly lower than those at the beginning of treatments (t= 3.26,3.17, 3.28, 2.92 and 3.12 respectively; P<0.01). Meanwhile, their clinical symptoms improved, sputum smear negative, lesions on chest X-ray resolved and the cavity shrinked or closed. Conclusions TNF-α, sTNF-R Ⅰ, IL-1β and IL-1 receptor are likely to be involved in the immunopathogenesis of tuberculosis. Detection of TNF-α, sTNF-R Ⅰ, IL-1β and IL-1 receptor levels in the serum and BALF is helpful to understand the activity of disease, determine the clinical pattern of disease,assess the prognosis of disease and monitor the therapeutic effect in patients with pulmonary tuberculosis.
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Objective To investigate the expression of the interleukin-1 receptor(IL-1R)Ⅰ,IL-1RⅡand IL-1R accessory protein(IL-1RAcP)in osteoarthritis and analyse their biological significance.Methods Immunohistochemistry and reverse transcription-polymerase chain raction(RT-PCR)were adopted to detect the expression of IL-1RⅠ,IL-1RⅡand IL-1RAcP on the synovium of 107 OA patients.Results Immunohis- tochemistry showed strong positive expression of IL-1RⅠand IL-1RAcP,and positive expression of IL-1RⅡ. The expression was distributed in lining cells,monocyts and vascular endothelial cells of the sublining area, but all of them were negative or weak positive in normal synoviums.RT-PCR showed the expression of IL-1RⅠ,IL-1RⅡand IL-1RAcP in OA synoviums was significantly enhanced than normal synoviums (P＜0.05),and the expression of IL-1RⅠwas significantly enhanced than IL-1RⅡ(P＜0.05),but no sig- nificant difference with IL-1RAcP(P＞0.05).In stageⅡandⅢOA synoviums,the expression of IL-1RⅠand IL-1 RAcP had no significant difference with normal synoviums(P＞0.05).The expression of IL-1RⅡin stageⅢOA synoviums was significantly enhanced than normal(P＜0.05).Conclusion IL-1RⅠ,IL-1RⅡand IL-1RAcP play significant roles in the pathogenesis of OA,especially IL-1RⅠand IL-1RAcP.But their increase is only observed in the early stage of OA.These suggest that they may have no association with the development of OA and have no direct association with the severity of OA.OA can be cured by interrupting the signal transduction path in which IL-1 has played biological roles.
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Objective: To develop a reporter gene system based on transient transfections with a NF-?B responsive reporter gene to detect the bioactivity of IL-1? and IL-1 receptor antagonist.Methods: NF-?B reporter and Dual-Luciferase assays were applied to measure the bioactivity of IL-1? and IL-1 receptor antagonist in mouse EL4 cells(some subclones of EL4 cells expressed high level of IL-1 receptor on cell surface).pNF-?B-luc and pRL-TK, used as an internal control,were co-transfected into EL4 cells and then the IL-1? was added.Results: The results indicated that IL-1? was able to induce the expression of this luciferase,which could be blocked by IL-1 receptor antagonist. The optimal dose of IL-1? was 5(?g/L) in Dual-Luciferase assay,whose bioactivity can be effectively inhibited by IL-1ra at 50 ?g/L.Conclusion: We have established a new method to detect the bioactivity of IL-1? and IL-1 receptor antagonist,which can give repeatable results.
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Objective To investigate the response of retinal ganglion cells (RGC)in detached and reattached retina in adult rats, and the effect of IL-1beta antibody and IL-1Ra on the loss of RGC. Methods A total of 73 Sprague-Dawley (SD) rats were subretinally injected with healon GV(1.4% hyaluronate)and retrograde labeled with fluorogold (FG), and 10 ng IL-1Ra and 500 ng IL-1beta antibody were injected into the subretinal space combined with healon GV. The retinal flakes were observed under the fluoroscope and the number of RGC was counted 2 hours, 1, 3, 5, 7, 10, 20, 50, and 90 days after detachment; 10 days after detachment and 30 days after reattachement; 90 days after detachment and 20 days after reattachement, and 1 and 10 days after injection with IL-1beta antibody and IL-1Ra,respectively. And the control group was only developed an intraocular injection of the same valume of healon GV. Result Two hours after detachment, the RGC loss was found, reached the peak at first day, and decreased gradually. RGC loss was also found in the non-detached area. The reattachment 10 days after detachment (early reattachment) stopped the loss of RGC, and the reattachment 90 days after detachment (late reattachment) promoted the loss, which rested on a certain level. Subretinal space injection of IL-1Ra and IL-1beta antibody decreased the loss of RGCs in the detached retina. Conclusion The RGCs loss were found both in the detached and attached retina. Early reattachment may stop the loss of RGC, and late reattachment may promote the loss. Both IL-1beta antibody and IL-1Ra have neuroprotective effect on RGC.