Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.
Humans ; 3' Untranslated Regions ; Arthritis, Gouty/genetics* ; Interleukin-1beta/genetics* ; Interleukin-8 ; Luciferases ; MicroRNAs/genetics* ; Tumor Necrosis Factor-alpha

BACKGROUNDChai Lai Prescription is a Chinese herbal compound which is used to sooth the liver, strengthen the spleen and harmonize the stomach for descending adverse Qi. We initiated the study to investigate its mechanism of treating in vitro rabbit reflux esophagitis models.

METHODSAdult male Japanese white rabbits, weighing 1.8-2.2 kg, were divided into five groups of three each, which were: normal control group (Krebs buffer, pH7.4), esophagitis model group (Krebs buffer, pH5.8), esophagitis model proup+low-dose Chinese herbal medicine protection group (0.6 mg × ml(-1)× kg(-1)), esophagitis model group+moderate-dose Chinese herbal medicine protection group (6 mg × ml(-1)× kg(-1)), esophagitis model group+high-dose Chinese herbal medicine protection group (60 mg × ml(-1)×kg(-1)). The RT-PCR method was used to test the influence of Chai Lai Prescription on IL-1 and IL-6 in in vitro rabbit models of esophagitis. We treated the in vitro models with different doses of Chinese herbal medicine.

RESULTSEsophageal mucosa were filled with various liquids. IL-6 and IL-1β mRNA expression was increased in rabbit esophageal mucosa stimulated with acid. Chinese herbal medicine significantly reduced the levels of IL-6 and IL-1β mRNA expression in the in vitro cultured rabbit esophageal mucosa. Using Chinese herbal medicine to treat in vitro models of RE, we found that the IL-6 and IL-1β mRNA expression levels went down, near to or lower than the normal control levels, compared with the group treated with acidified buffer solution.

CONCLUSIONSChai Lai Prescription lowered the IL-1β and IL-6 cytokine mRNA levels and protected the esophageal mucosa in the in vitro models of reflux esophagitis, suggesting that the traditional Chinese herbal compound may be able to treat reflux esophagitis by inhibiting the its inflammatory mediators.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Esophagitis, Peptic ; drug therapy ; metabolism ; Interleukin-1beta ; genetics ; Interleukin-6 ; genetics ; Male ; Rabbits

Osteoarthritis(OA) is one of the most common joint diseases. As Chinese society enters the age of aging, the incidence of OA has been soar year by year, and research on its pathogenesis has been continuously valued by researchers. Studies have found that inflammatory cytokines, mainly interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), were responsible for the construction of OA inflammatory networks. It was also found that the overexpression of proteases, mainly matrix metalloproteinases(MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), was the direct cause of OA cartilage deficiency. What's more, signaling pathways such as stromal cell derived factor-1 (SDF-1) and Wnt, chondrocytic senescence and the senescence-associated secretory phenotype (SASP), chondrocyte apoptosis and autophagy, and estrogen all play significant roles in OA pathogenesis. This paper extensively reviews the research literature relevant to the pathogenesis of OA in recent years, and systematically expounds the pathogenesis of OA from two aspects:molecular level and cell level. At the end of the paper, we discussed and predicted some potential directions in the future clinical diagnosis and treatment of OA.
Cartilage ; Cartilage, Articular ; Chondrocytes ; Humans ; Interleukin-1beta ; Osteoarthritis/genetics* ; Signal Transduction ; Tumor Necrosis Factor-alpha

OBJECTIVETo investigate whether interleukin-1 beta (IL-1beta ) and interleukin-1 receptor antagonist (IL-1RA) gene polymorphisms are associated with endometriosis (EMs) in Chinese women.

METHODSOne hundred and thirty-eight patients with EMs and 100 women without EMs were enrolled in the study. Polymorphisms for IL-1 beta-511 promoter, IL-1 beta exon 5, and IL-1RA were detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).

RESULTThere were no significant differences about the distribution of the genotypes and alleles of IL-1 beta -511 promoter and IL-1 beta exon 5 in two groups (P > 0.05). The frequencies of A1/A1, A1/A2, A1/A4 and A2/A2 of IL-1RA gene were 84.1 %, 12.3 %, 2.9 % and 0.7 % in EMs and 95 % , 4 % ,1 % and 0 % in controls, respectively (P=0.042). The A1, A2 and A4 alleles were 91.7 % , 6.9 % and 1.4 % in EMs and 97.5 % , 2 % and 0.5 % in controls (P=0.019). In comparison with the reference genotype, the wild A1/A1 homozygote, the odds ratio for A1/A2 was 3.48 (95 % CI: 1.13 - 10.69). Compared with the A1 allele, the odds ratio for the A2 allele was 3.66 (95 % CI: 1.23 - 10.94).

CONCLUSIONAssociation between the IL-1 beta-511 promoter,IL-1 beta exon 5 polymorphisms and EMs in China is not found. However, the A2 allele of IL-1RA gene may be one of the risk factors for the Chinese women in Zhejiang Province to suffer EMs.

Adult ; Alleles ; China ; Endometriosis ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Interleukin 1 Receptor Antagonist Protein ; genetics ; Interleukin-1beta ; genetics ; Polymorphism, Genetic

Cervical cancer is almost invariably associated with infection by human papillomavirus. It is believed that the host genetic factors such as inflammation-induced cytokines may play a role in cervical carcinogenesis. The IL1B gene, encoding IL-1beta cytokine, contains several single nucleotide polymorphisms. One of them which is in the positions -511 (C-T) related with promoter region has been associated with increased IL-1beta production and with increased risk of developing a number of inflammatory diseases and gastric carcinoma. We assessed the association between the IL1B -511 polymorphism and cervical cancer risk in a hospital-based case-control study among 546 Korean women (182 cases; 364 age-matched controls). The allele frequencies of the case subjects (C, 0.42; T, 0.58) were not significantly different from those of control subjects (C, 0.43; T, 0.57). Control subjects were in Hardy-Weinberg equilibrium. The carriers with -511 C/T or T/T genotypes were at higher risk of cervical cancer with odds ratio of 2.42 (95% CI 1.31-4.46, p<0.005). However, there was no difference of cervical cancer risk between C/T heterologous genotypes and T/T homologous genotypes. In conclusion, in Korean population, IL1B -511 C/C genotypes were significantly associated with a decreased risk of cervical cancer.
Uterine Cervical Neoplasms/etiology/*genetics ; *Polymorphism, Genetic ; Interleukin-1beta/*genetics ; Humans ; Genotype ; Genetic Predisposition to Disease ; Female ; Case-Control Studies

OBJECTIVEDespite substantial research efforts worldwide, the role of inflammatory cytokine IL-1β in the onset of febrile seizures (FS) remains controversial. The aim of this study was to assess the relationship between rs16944 polymorphism of the IL-1β-511T gene and occurrence of simple FS in a sample of Han children in northern China.

METHODSThe IL-1β-511T gene rs16944 was genotyped by SNaPshot SNP technique in 141 FS children and 130 healthy control subjects. The genotypic and allelic frequencies in the two groups were comparatively analyzed.

RESULTSThere were no significant differences in genotypic and allelic frequencies of rs16944 polymorphism of the IL-1β-511T gene between FS patients and control subjects (P>0.05).When the clinical data on A/A, A/G and G/G genotypes of the rs16944 polymorphism in FS patients, there was statistically significant difference in age of first onset (χ(2)=19.491, P<0.01), temperature of first onset (χ(2)=9.317, P<0.05) and family history of FS (χ(2)=26.798, P<0.01).

CONCLUSIONSThere is no association between rs16944 polymorphism of the IL-1β-511T gene and the incidence of FS in Han children in Northern China. However, the differences in genotypes of this polymorphism might be associated with pathogenesis and prognosis of simple FS in the population studied.

Child, Preschool ; China ; ethnology ; Female ; Humans ; Infant ; Interleukin-1beta ; genetics ; Male ; Polymorphism, Single Nucleotide ; Seizures, Febrile ; genetics

OBJECTIVETo investigate the association between interleukin (IL)-1β genetic polymorphisms and obstructive sleep apnea syndrome (OSAS).

METHODSTotally 850 individuals with hypertension were included. All of them were checked by polysomnography in the Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region from January to December in 2010. According to the results of polysomnography, these subjects were divided into non-OSAS group (n=225)and OSAS group (n=625). Genetic variations were sequenced and screened at loci over functional region of IL-1β gene in 96 patients with severe OSAS.The typical loci were selected for genotyping by TaqMan-polymerase chain reaction in 850 subjects.

RESULTSOne novel and 5 known variations in the IL-1β gene were identified, and then three representative mutation loci were selected for genotyping.The allele frequency distribution of rs1143633 was significantly different between the OSAS and non-OSAS groups in the total and male populations (χ(2)=9.258, P=0.002;χ(2)=5.119, P=0.024, respectively). Although the parameters of sleep apnea monitoring showed no significant difference in individuals with CC, CT, and TT genotypes of rs1143633 in total, male, and female populations (P>0.05), the median of the apnea hypopnea index of CT genotype was significantly higher than that of CC and TT in total and male populations and the mean of the lowest blood oxygen saturation increased in individuals with CC, CT, and TT genotypes of rs1143633 in total and male populations.Haplotype was no significantly associated with OSAS in total,male,and female populations(P>0.05).Logistic regression analysis showed that CT genotype of rs1143633 variation was a risk factor for OSAS in total and male populations (OR=1.574,95% CI=1.061-2.437,P=0.042;OR=1.887,95% CI=1.091- 3.265,P=0.023).

CONCLUSIONThe rs1143633 polymorphism in IL-1β gene may be associated with OSAS.

Adult ; Female ; Genetic Variation ; Genotype ; Humans ; Interleukin-1beta ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Sleep Apnea, Obstructive ; genetics

OBJECTIVETo investigate the correlation between polymorphism at position -511C/T in the promoter region of interleukin 1B (IL1B) and the severity of coronary heart disease (CHD).

METHODSThe polymerase chain reaction-restriction fragment length polymorphism technique was applied to analyze the polymorphisms of IL1B -511C/T in 127 patients with CHD and 152 controls. And the serum level of lipoproteins was detected by enzymology method.

RESULTSThe distribution of IL1B -511C/T polymorphism between acute coronary syndrome (ACS) patients and controls was significantly different (chi-square test=5.72, P<0.01). CT and TT genotype carriers were in increased risk of ACS with more double ratio to CC genotype (OR=2.56, 95%CI=1.17-5.59). In CHD group, total cholesterol and low density lipoprotein-cholesterol levels of patients with CT and TT genotypes (6.09+/-0.97 mmol/L and 3.97+/-0.92 mmol/L) were significantly higher than those of patients with CC genotype (5.12+/-0.56 mmol/L and 2.87+/-0.71 mmol/L, P<0.05).

CONCLUSIONThe polymorphism at position -511C/T in IL1B is associated with the severity of CHD, and the DNA variation at this position may affect the secretion of IL1B, and aggravate the reaction of inflammation and dyslipoidemia.

Coronary Disease ; genetics ; Female ; Humans ; Interleukin-1 ; genetics ; Interleukin-1beta ; Male ; Middle Aged ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; genetics ; Severity of Illness Index

OBJECTIVETo evaluate the correlation between the gene polymorphism of IL-1beta-511 or IL-1RN VNTR and the risk of coronary heart disease (CHD).

METHODSThe patient-control studies on the association of IL-1=-511 or IL-1RN VNTR gene polymorphism with the risk of CHD were searched according to the inclusion criteria. Heterogeneity tests were conducted for the data from each study before Meta-analysis.

RESULTSFor the 7 studies addressing the correlation between IL-1beta-511 polymorphism and the susceptibility of CHD, the pooled odds ratio was about 1.04 with 95% CI of 0.93-1.18 (Z=0.71, P=0.48). For the 5 studies of the correlation between IL-1RN VNTR polymorphism and the susceptibility of CHD, the pooled odds ratio was about 1.01 and the 95% CI was 0.78-1.17 (Z=0.08, P=0.93).

CONCLUSIONThe gene polymorphism of IL-1beta-511 or IL-1RN VNTR has no correlation to the susceptibility of CHD, but is associated with in the disease development and clinical phenotype.

Alleles ; Coronary Disease ; genetics ; Gene Frequency ; Genotype ; Humans ; Interleukin 1 Receptor Antagonist Protein ; genetics ; Interleukin-1beta ; genetics ; Minisatellite Repeats ; Polymorphism, Genetic ; Risk Factors

BACKGROUNDInterleukin 1beta (IL-1beta) is the principal mediator in the pathogenesis of rheumatoid arthritis. Continuous injection of interleukin 1beta (IL-1beta) into the knee articular cavities of animals can induce models that resemble rheumatoid arthritis. The objective of this study was to evaluate the feasibility of local recombinant retrovirus viral interleukin 10 (rRV-vIL-10) gene transfer treatment of a rabbit model of arthritis induced by IL-1beta.

METHODSAn hIL-1beta-induced rabbit rheumatoid arthritis model was established using the MFG-hIL-1beta-neo-HIG-82 cell line, which is capable of continuous secretion of hIL-1beta. After transfecting the rabbit synovial fibroblast cell line (MFG-hIL-1beta-neo-HIG-82) with rRV-vIL-10, G418 was then added to identify the positive clone. The rRV-vIL-10 positive clone was injected into the established rabbit rheumatoid arthritis model through intra-articular injection. Successful gene transfer was determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The levels of IL-1beta before and after treatment were determined by enzyme- linked immunosorbent assay.

RESULTSRetrovirus vector was an effective vector both to synoviocytes in vitro and synovium tissue in vivo as confirmed by RT-PCR and immunohistochemistry. The rabbit arthritis model treated with rRV-vIL-10 showed a dramatic remission of arthritis and a decline in the level of cytokines such as IL-1beta.

CONCLUSIONSRetrovirus-mediated transfection of vIL-10 successfully transferred the gene into rabbit synovium ex vivo and was able to suppress intra-articular inflammation response to IL-1beta.

Animals ; Arthritis ; therapy ; Disease Models, Animal ; Female ; Genetic Therapy ; Genetic Vectors ; Interleukin-10 ; analysis ; genetics ; Interleukin-1beta ; toxicity ; RNA, Messenger ; analysis ; Rabbits ; Retroviridae ; genetics