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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(2): 141-145, 2020 Feb.
Artículo en Chino | MEDLINE | ID: mdl-32051081

RESUMEN

OBJECTIVE: To study the association of single nucleotide polymorphisms (SNPs) of interleukin-23 receptor (IL-23R) rs10889677, interleukin-17A (IL-17A) rs227591, and interleukin-17F (IL-17F) rs763780 with necrotizing enterocolitis (NEC) in Chinese Han preterm infants. METHODS: A total of 100 Chinese Han preterm infants with NEC who were admitted to the neonatal intensive care unit from January 2017 to January 2019 were prospectively enrolled. Of the 100 preterm infants, 63 had stage II NEC and 37 had stage III NEC. A total of 100 preterm infants, matched for age and sex, were selected as the control group. PCR and Sanger sequencing were used to determine the SNPs of rs10889677, rs2275913, and rs763780. An unconditional logistic regression analysis was used to investigate the association of SNPs with NEC susceptibility and severity. RESULTS: The genotype and allele frequencies of rs10889677 and rs2275913 had no influence on the development of NEC (P>0.05). The genotype of rs763780 had no influence on the development of NEC (P>0.05), but the risk of NEC in the infants carrying C allele was 1.652 times that in those carrying T allele (95%CI: 1.052-2.695, P<0.05). The risk of NEC in the infants carrying TC+CC genotype was 1.856 times that in those carrying TT genotype (95%CI: 1.045-3.201, P<0.05). The risk of stage III NEC in the infants carrying TC+CC genotype was 2.965 times that in those carrying TT genotype (95%CI: 1.052-6.330, P<0.05). The risk of stage III NEC in the infants carrying C allele was 2.363 times that in those carrying T allele (95%CI: 1.034-4.093, P<0.05). CONCLUSIONS: The SNPs of IL-23R rs10889677 and IL-17A rs2275913 are not associated with the susceptibility to NEC in Chinese Han preterm infants, while TC+CC genotype and C allele of IL-17F rs763780 are associated with the susceptibility to NEC and the severity of NEC.


Asunto(s)
Enterocolitis Necrotizante , Interleucina-17/genética , Polimorfismo de Nucleótido Simple , Receptores de Interleucina/genética , Grupo de Ascendencia Continental Asiática , Estudios de Casos y Controles , Enterocolitis Necrotizante/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Recién Nacido , Recien Nacido Prematuro
2.
Gut ; 69(2): 264-273, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31097538

RESUMEN

OBJECTIVE: The interleukin (IL)23 pathway contributes to IBD pathogenesis and is being actively studied as a therapeutic target in patients with IBD. Unexpected outcomes in these therapeutic trials have highlighted the importance of understanding the cell types and mechanisms through which IL23 regulates immune outcomes. How IL23 regulates macrophage outcomes and the consequences of the IL23R R381Q IBD-protective variant on macrophages are not well defined; macrophages are key players in IBD pathogenesis and inflammation. DESIGN: We analysed protein and RNA expression, signalling and localisation in human monocyte-derived macrophages (MDMs) through western blot, ELISA, real-time PCR, flow cytometry, immunoprecipitation and microscopy. RESULTS: IL23R was critical for optimal levels of pattern-recognition receptor (PRR)-induced signalling and cytokines in human MDMs. In contrast to the coreceptor IL12Rß1, IL23 induced dynamic IL23R cell surface regulation and this required clathrin and dynamin-mediated endocytosis and endocytic recycling-dependent pathways; these pathways were essential for IL23R-mediated outcomes. The IBD-protective IL23R R381Q variant showed distinct outcomes. Relative to IL23R R381, HeLa cells expressing IL23R Q381 showed decreased IL23R recycling and reduced assembly of IL23R Q381 with Janus kinase/signal transducer and activator of transcription pathway members. In MDMs from IL23R Q381 carriers, IL23R accumulated in late endosomes and lysosomes on IL23 treatment and cells demonstrated decreased IL23R- and PRR-induced signalling and cytokines relative to IL23R R381 MDMs. CONCLUSION: Macrophage-mediated inflammatory pathways are key contributors to IBD pathogenesis, and we identify an autocrine/paracrine IL23 requirement in PRR-initiated human macrophage outcomes and in human intestinal myeloid cells, establish that IL23R undergoes ligand-induced recycling, define mechanisms regulating IL23R-induced signalling and determine how the IBD-protective IL23R R381Q variant modulates these processes.


Asunto(s)
Citocinas/inmunología , Enfermedades Inflamatorias del Intestino/inmunología , Macrófagos/inmunología , Receptores de Interleucina/inmunología , Comunicación Autocrina/inmunología , Endocitosis/inmunología , Endosomas/inmunología , Variación Genética , Humanos , Inmunidad Innata/genética , Inmunidad Innata/inmunología , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/prevención & control , Interleucina-23/inmunología , Janus Quinasa 2/metabolismo , Comunicación Paracrina/inmunología , Receptores de Interleucina/genética , Receptores de Reconocimiento de Patrones/inmunología , Transducción de Señal/inmunología
3.
Int J Mol Sci ; 20(17)2019 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-31454926

RESUMEN

Interleukin (IL)-23 is considered an effective therapeutic target for the treatment of psoriasis because of the crucial role of the IL-23/IL-17 axis in the pathogenesis of psoriasis, and it has recently been reported to be involved in ILC3 cell differentiation. In this study, we report that eukaryotically expressed rhIL23R-CHR/Fc, as an endogenous extracellular receptor analogue, could be a natural antagonist in an imiquimod (IMQ)-induced psoriasis-like mouse model, including the antagonizing effect of suppressed inflammation in the skin lesion, decreased production of pro-inflammatory cells, and reduced the expression of pro-inflammatory factors. The rhIL23R-CHR/Fc fusion protein inhibits both innate immune and adaptive immune-mediated inflammatory responses. These findings shed light on rhIL23R-CHR/Fc as a promising candidate therapy for the treatment of psoriasis.


Asunto(s)
Inmunidad Innata/efectos de los fármacos , Psoriasis/etiología , Psoriasis/metabolismo , Proteínas Recombinantes de Fusión/farmacología , Células Th17/efectos de los fármacos , Células Th17/inmunología , Células Th17/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Femenino , Humanos , Fragmentos Fc de Inmunoglobulinas/genética , Linfocitos/inmunología , Linfocitos/metabolismo , Ratones , Dominios y Motivos de Interacción de Proteínas , Psoriasis/tratamiento farmacológico , Psoriasis/patología , Receptores de Interleucina/química , Receptores de Interleucina/genética , Proteínas Recombinantes de Fusión/genética , Piel/efectos de los fármacos , Piel/inmunología , Piel/metabolismo , Piel/patología , Células Th17/citología
4.
Infect Immun ; 87(11)2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31451621

RESUMEN

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia worldwide, and interleukin-22 (IL-22) helps contain pneumococcal burden in lungs and extrapulmonary tissues. Administration of IL-22 increases hepatic complement 3 and complement deposition on bacteria and improves phagocytosis by neutrophils. The effects of IL-22 can be tempered by a secreted natural antagonist, known as IL-22 binding protein (IL-22BP), encoded by Il22ra2 To date, the degree to which IL-22BP controls IL-22 in pulmonary infection is not well defined. Here, we show that Il22ra2 inhibits IL-22 during S. pneumoniae lung infection and that Il22ra2 deficiency favors downregulation of oxidative phosphorylation (OXPHOS) genes in an IL-22-dependent manner. Il22ra2-/- mice are more resistant to S. pneumoniae infection, have increased IL-22 in lung tissues, and sustain longer survival upon infection than control mice. Transcriptome sequencing (RNA-seq) analysis of infected Il22ra2-/- mouse lungs revealed downregulation of genes involved in OXPHOS. Downregulation of this metabolic process is necessary for increased glycolysis, a crucial step for transitioning to a proinflammatory phenotype, in particular macrophages and dendritic cells (DCs). Accordingly, we saw that macrophages from Il22ra2-/- mice displayed reduced OXPHOS gene expression upon infection with S. pneumoniae, changes that were IL-22 dependent. Furthermore, we showed that macrophages express IL-22 receptor subunit alpha-1 (IL-22Ra1) during pneumococcal infection and that Il22ra2-/- macrophages rely more on the glycolytic pathway than wild-type (WT) controls. Together, these data indicate that IL-22BP deficiency enhances IL-22 signaling in the lung, thus contributing to resistance to pneumococcal pneumonia by downregulating OXPHOS genes and increasing glycolysis in macrophages.


Asunto(s)
Interleucinas/metabolismo , Neumonía Neumocócica/metabolismo , Receptores de Interleucina/metabolismo , Animales , Línea Celular , Susceptibilidad a Enfermedades , Células Epiteliales/fisiología , Regulación de la Expresión Génica , Interleucinas/genética , Antígenos Comunes de Leucocito , Pulmón/citología , Macrófagos/metabolismo , Ratones , Ratones Noqueados , Oxidación-Reducción , Fosforilación , Neumonía Neumocócica/inmunología , Receptores de Interleucina/genética , Streptococcus pneumoniae
5.
J Orthop Surg Res ; 14(1): 210, 2019 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-31291973

RESUMEN

BACKGROUND: Thoracic ossification of the posterior longitudinal ligament (T-OPLL) can cause thoracic spinal stenosis, which results in intractable myelopathy and radiculopathy. The etiology of T-OPLL is unknown and the condition is difficult to treat surgically. Whole-genome sequencing identified a genetic variant at rs199772854 of the interleukin 17 receptor C (IL17RC) gene as a potentially pathogenic locus associated with T-OPLL. We aimed to determine whether the rs199772854A site mutation causes abnormal expression of the IL17RC in Han Chinese patients with T-OPLL and predict the possible pathogenic mechanisms of T-OPLL. Analyses were performed to determine whether IL17RC is involved in the pathogenicity of T-OPLL. METHODS: Peripheral blood and OPLL tissue were collected from a total of 72 patients with T-OPLL disease (36 patients carrying the rs199772854A site mutation in IL17RC and 36 wild-type patients). The expression of IL17RC was analyzed by enzyme-linked immunosorbent assay, reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, and Western blotting. RESULTS: rs199772854A mutation resulted in markedly increased IL17RC gene expression levels in peripheral blood samples and the OPLL tissue obtained following clinical surgery (P < 0.05). CONCLUSIONS: The results suggest that the rs199772854A site mutation of IL17RC can significantly increase the expression of IL17RC. The IL17RC gene rs199772854A site polymorphism is a potential pathogenic mutation in T-OPLL disease, which may be associated with the occurrence of T-OPLL.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Osificación del Ligamento Longitudinal Posterior/sangre , Osificación del Ligamento Longitudinal Posterior/genética , Receptores de Interleucina/sangre , Receptores de Interleucina/genética , Vértebras Torácicas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osificación del Ligamento Longitudinal Posterior/diagnóstico , Receptores de Interleucina/biosíntesis , Estudios Retrospectivos
6.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(4): 327-332, 2019 Apr.
Artículo en Chino | MEDLINE | ID: mdl-31167692

RESUMEN

Objective To investigate the role of interleukin 20 receptor 2 (IL-20R2) family signaling pathway in psoriasis via imiquimod (IMQ) treatment. Methods IL-20R2 knockdown (IL-20R2-/-) mice and wild type IL-20R2+/+mice were used in this experiment. IL-20R2 mRNA in the skin tissue of the mice was detected by PCR sequencing and the IL-20R2 protein level was analyzed by Western blot analysis. We then established a psoriasis-like mouse model by topical treatment with IMQ, and body mass and skin lesions were recorded daily. In addition, HE staining was performed to observe the pathological changes of the skin. Results Compared with wild type IL-20R2+/+mice, the IL-20R2-/- mice showed lower levels of both IL-20R2 protein and mRNA in the skin tissue, also exhibited a markedly less pathological changes after IMQ induction. Conclusion Knockdown of IL-20R2 gene can inhibit the development of psoriasis induced by IMQ in mice.


Asunto(s)
Técnicas de Silenciamiento del Gen , Psoriasis/patología , Receptores de Interleucina/genética , Animales , Imiquimod , Ratones , Ratones Noqueados , Psoriasis/inducido químicamente
7.
Mol Carcinog ; 58(10): 1822-1831, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31197899

RESUMEN

Single nucleotide polymorphisms (SNPs) in interleukin-23 receptor (IL23R) are involved in the pathogenesis of many cancers and autoimmune diseases. IL23R gene is still controversial in the study of esophageal cancer. The aim of this research is to investigate the influence of IL23R SNPs on the risk of esophageal cancer. Five hundred six esophageal cancer and 507 controls frequency matched by age and gender were conducted, and the genotypes were determined by the Agena MassARRAY. Logistic regression analysis was used to evaluate the odd ratios (ORs) and 95% confidence intervals (CIs) of rs1884444 and rs6682925 with susceptibility of esophageal cancer. A total of 30 articles are eligible. Pooled ORs and the 95% CI were calculated using the random-effect model. Database predicts the expression of IL23R gene in esophageal cancer. IL23R rs1884444 allele G decreased the risk of esophageal cancer under allele, genotype, and additive models (allele model: OR = 0.82, 95% CI: 0.68-0.98, P = .032; genotype model: OR = 0.65, 95% CI: 0.44-0.97, P = .035; additive model: OR = 0.82, 95% CI: 0.68-0.98, P = .031). Meta-analysis shown that IL23R rs1884444 increased the risk of overall disease in allele model (OR = 1.16, 95% CI: 1.08-1.25, P < .001), and also increased the risk of gastrointestinal tumor (OR = 1.18, 95% CI: 1.05-1.31, P = .005). The database analysis showed that the expression of IL23R gene was upregulated in esophageal cancer tissues. IL23R rs1884444 may play an important role in the susceptibility of esophageal cancer.


Asunto(s)
Neoplasias Esofágicas/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Receptores de Interleucina/genética , Alelos , China , Neoplasias Esofágicas/patología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo
8.
Immunol Invest ; 48(6): 585-596, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31044631

RESUMEN

Inflammation plays a central role in the pathophysiology of acute pancreatitis (AP). We hypothesized that changes in the function of key components of the inflammatory cascade, caused by genetic polymorphisms, could determine the development and/or severity of AP. We studied the following polymorphisms in 269 patients: IL23R rs11209026, TNF rs1800629, RIPK2 rs42490, NOD2 rs9302752, MCP1 rs1024611 and NFKB1 rs28362491. The rs11209026 A allele was related to the presence of AP (p = 0.007261; OR = 1 .523). Epistasis analysis revealed that AP susceptibility was increased by interaction between IL23R rs11209026 and TNF rs1800629 (p = 1.205 × 10-5; ORinteraction = 4.031). The rs42490-G allele was associated with an increased risk of severe pancreatitis (p = 0.01583; OR = 2.736), severe or moderately severe pancreatitis (p = 0.04206; OR = 1.609), and death (p = 0.03226; OR = 3.010). In conclusion, these results point to a plausible role for genetic polymorphisms in IL23R and RIPK2 in the development and severity of AP.


Asunto(s)
Genotipo , Pancreatitis/genética , Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor/genética , Receptores de Interleucina/genética , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis/mortalidad , Polimorfismo de Nucleótido Simple , Riesgo , Índice de Severidad de la Enfermedad
9.
Artículo en Inglés | MEDLINE | ID: mdl-31052515

RESUMEN

It is suggested that IL-23/IL-17 axis and single nucleotide polymorphisms (SNPs) of IL23R may have crucial role in pathogenesis of Crohn's disease (CD). Thus, we sought to assess the IL23R SNPs contribution to susceptibility and phenotype of CD. We recruited 117 CD subjects and 117 controls from Poland and 30 CD subjects and 30 controls from Bosnia and Herzegovina (B&H). Two common IL23R SNPs: rs1004819, rs7517847 were genotyped using TaqMan SNP assays. In the Polish population it was found that allele rs1004819: A increases the risk of CD, while allele rs7517847: A is protective against disease development. In Poles the co-carriage of two IL23R risk genotypes was associated with increased risk of CD. A significantly increased risk of CD early onset was observed in Poles carrying at least one rs7517847: G allele. It was also found that IL23R SNPs may be associated with structuring/penetrating CD behavior, as alleles rs1004819: A and rs7517847: G were significantly less frequent in patients without complications, from Poland and B&H, respectively. Allele rs1004819: A was also significantly more frequent in Poles with penetrating CD. These results confirm IL23R SNPs contribution to CD susceptibility in the Polish population and suggest their impact on early age of onset and more severe disease course.


Asunto(s)
Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Receptores de Interleucina/genética , Adulto , Alelos , Bosnia y Herzegovina/epidemiología , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Polonia/epidemiología
10.
Immunity ; 50(5): 1289-1304.e6, 2019 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-31079916

RESUMEN

Pathogenic lymphocytes initiate the development of chronic inflammatory diseases. The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) (encoded by Csf2) is a key communicator between pathogenic lymphocytes and tissue-invading inflammatory phagocytes. However, the molecular properties of GM-CSF-producing cells and the mode of Csf2 regulation in vivo remain unclear. To systematically study and manipulate GM-CSF+ cells and their progeny in vivo, we generated a fate-map and reporter of GM-CSF expression mouse strain (FROG). We mapped the phenotypic and functional profile of auto-aggressive T helper (Th) cells during neuroinflammation and identified the signature and pathogenic memory of a discrete encephalitogenic Th subset. These cells required interleukin-23 receptor (IL-23R) and IL-1R but not IL-6R signaling for their maintenance and pathogenicity. Specific ablation of this subset interrupted the inflammatory cascade, despite the unperturbed tissue accumulation of other Th subsets (e.g., Th1 and Th17), highlighting that GM-CSF expression not only marks pathogenic Th cells, but that this subset mediates immunopathology and tissue destruction.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Interleucina-1beta/inmunología , Subunidad p19 de la Interleucina-23/inmunología , Células TH1/inmunología , Células Th17/inmunología , Animales , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Inflamación/genética , Inflamación/patología , Interferón gamma/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores CXCR6/metabolismo , Receptores de Interleucina/genética , Receptores de Interleucina/inmunología , Receptores Tipo I de Interleucina-1/genética , Receptores Tipo I de Interleucina-1/inmunología , Factor de Necrosis Tumoral alfa/metabolismo
11.
J Clin Lab Anal ; 33(6): e22893, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31074535

RESUMEN

BACKGROUND: Polymorphisms in IL-17A and IL-23R may affect the expression of these genes and could contribute to a patient's susceptibility to coronary artery disease (CAD). Although this association was investigated by previous studies, the relationship remains unclear. METHOD: We conducted this hospital-based case-control study to determine whether polymorphisms in these two genes could be associated with a risk of CAD. A total of 191 patients and 131 controls, as determined by SXscore, were enrolled in this study. The genotyping was performed with the Sequenom MassARRAY platform. RESULTS: The results showed that that the FPG and HbA1C levels were higher in patients with CAD than in the controls. In addition, the HDL and ApoA1 levels were significantly higher in the controls than in the cases. In contrast, the Lp(a) level was significantly lower in the controls than in the patients. The IL-17A rs2275913 and IL-23R rs6682925 polymorphisms were associated with an increased risk of CAD (rs2275913: AA vs GG: crude OR = 2.16, 95% CI = 1.08-4.30; AG/AA vs GG: crude OR = 1.81, 95% CI = 1.04-3.15; rs6682925 CC vs TT: crude OR = 1.91, 95% CI = 1.00-3.63). The subgroup analysis by SXscore revealed that the IL-23R rs6682925 polymorphism (CT/CC vs TT: crude OR = 3.72, 95% CI = 1.19-11.66) was associated with an increased risk of CAD in patients with a high SXscore. CONCLUSION: This study suggested that T2DM, Lp(a), HDL-c, and ApoA1 were risk factors of CAD and that the IL-17A rs2275913 and IL-23R rs6682925 polymorphisms may contribute to susceptibility to CAD.


Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Interleucina-17/genética , Polimorfismo de Nucleótido Simple , Receptores de Interleucina/genética , Anciano , Grupo de Ascendencia Continental Asiática , Glucemia/análisis , Estudios de Casos y Controles , HDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/etiología , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Hemoglobina A Glucada/análisis , Humanos , Lipoproteínas HDL/sangre , Masculino , Persona de Mediana Edad
12.
Int J Mol Sci ; 20(10)2019 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-31108847

RESUMEN

Of the three interleukin-22 binding protein (IL-22BP) isoforms produced by the human IL22RA2 gene, IL-22BPi2 and IL-22BPi3 are capable of neutralizing IL-22. The longest isoform, IL-22BPi1, does not bind IL-22, is poorly secreted, and its retention within the endoplasmic reticulum (ER) is associated with induction of an unfolded protein response (UPR). Therapeutic modulation of IL-22BPi2 and IL-22BPi3 production may be beneficial in IL-22-dependent disorders. Recently, we identified the ER chaperones GRP94 and cyclophilin B in the interactomes of both IL-22BPi1 and IL-22BPi2. In this study, we investigated whether secretion of the IL-22BP isoforms could be modulated by pharmacological targeting of GRP94 and cyclophilin B, either by means of geldanamycin, that binds to the ADP/ATP pocket shared by HSP90 paralogs, or by cyclosporin A, which causes depletion of ER cyclophilin B levels through secretion. We found that geldanamycin and its analogs did not influence secretion of IL-22BPi2 or IL-22BPi3, but significantly enhanced intracellular and secreted levels of IL-22BPi1. The secreted protein was heterogeneously glycosylated, with both high-mannose and complex-type glycoforms present. In addition, cyclosporine A augmented the secretion of IL-22BPi1 and reduced that of IL-22BPi2 and IL-22BPi3. Our data indicate that the ATPase activity of GRP94 and cyclophilin B are instrumental in ER sequestration and degradation of IL-22BPi1, and that blocking these factors mobilizes IL-22BPi1 toward the secretory route.


Asunto(s)
Benzoquinonas/farmacología , Ciclofilinas/metabolismo , Ciclosporina/farmacología , Lactamas Macrocíclicas/farmacología , Glicoproteínas de Membrana/metabolismo , Receptores de Interleucina/metabolismo , Sitios de Unión/efectos de los fármacos , Ciclofilinas/química , Retículo Endoplásmico/metabolismo , Perfilación de la Expresión Génica , Glicosilación , Células HEK293 , Humanos , Glicoproteínas de Membrana/química , Monocitos/metabolismo , Unión Proteica/efectos de los fármacos , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Proteolisis , Receptores de Interleucina/química , Receptores de Interleucina/genética
13.
J Assist Reprod Genet ; 36(7): 1523-1536, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31123953

RESUMEN

PURPOSE: Pre-eclampsia is a relatively common pregnancy disorder. Serum concentrations of certain pro-inflammatory molecules and cytokines like interleukin-23 may affect the pathogenesis of pre-eclampsia. The interleukin-23 receptor (IL-23R) gene plays an important role in the progression of inflammatory and autoimmune diseases and IL-23 polymorphisms might influence the susceptibility of pre-eclampsia. The aim of the recent study was to establish the association between IL-23R gene polymorphisms and the susceptibility for developing of pre-eclampsia. METHODS: One hundred and fifty-eight pregnant patients with pre-eclampsia and 153 controls were genotyped using RFLP-PCR and AS-PCR. Also, an in silico analysis was performed to predict possible effects of these variations on IL-23R mRNA and protein structures. RESULTS: The frequency of the AG genotype of rs11209026 is related to a higher risk of pre-eclampsia. The mutant C and A allele in rs10889677 and rs11209026 SNPs, respectively, are correlated with the risk of pre-eclampsia and they are more frequent in severe late onset PE. We found higher frequency of the haplotype CG in patients with pre-eclampsia in comparison to healthy controls, as well as, the CG haplotype frequency significantly increased the risk of PE in severe, early onset, and late onset sub-groups. The results of computational analysis predicted rs11209026 and rs10889677 SNPs as functional variations, which can influence IL-23R mRNA and protein. CONCLUSIONS: The results of present study show positive association between polymorphisms in the IL-23R gene and pre-eclampsia. Therefore, the presence of IL-23R rs11209026, rs10889677 polymorphism might be markers for the genetic susceptibility to pre-eclampsia.


Asunto(s)
Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Preeclampsia/genética , Receptores de Interleucina/genética , Adulto , Femenino , Haplotipos/genética , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genética , Preeclampsia/patología , Embarazo , Factores de Riesgo
14.
Artif Cells Nanomed Biotechnol ; 47(1): 951-956, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30942097

RESUMEN

OBJECTIVE: This meta-analysis was aimed to verify the influences of interleukin 23 receptor (IL-23R) rs11209026 and rs2201841 polymorphisms on the susceptibility of rheumatoid arthritis (RA). METHODS: We searched potentially relevant studies on the relationships of IL-23R gene rs11209026 and rs2201841 polymorphisms with RA susceptibility from PubMed (Medline), CNKI and EMBASE web databases. Crude odds ratios (ORs) along with 95% confidence intervals (95% CIs) were calculated to assess the strength of association through the fixed- or random-effects model. RESULTS: Eight published articles containing 5544 RA patients and 5532 health individuals were included in our meta-analysis. In total analysis, we found IL-23R gene rs11209026 polymorphism was not related to RA susceptibility in all genetic models, but there was a significant association between rs2201841 polymorphism and RA susceptibility under G vs. A model. In stratified analysis by ethnicity, an increased RA susceptibility was detected for rs2201841 polymorphism in Caucasian group. CONCLUSION: The results of meta-analysis indicated that IL-23R gene rs2201841 polymorphism might be a susceptible factor for RA under G vs. A model, especially in Caucasian population.


Asunto(s)
Artritis Reumatoide/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo Genético , Receptores de Interleucina/genética , Alelos , Humanos
15.
World J Gastroenterol ; 25(8): 1012-1023, 2019 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-30833806

RESUMEN

BACKGROUND: The lethal-7 (let-7) family members and their targets are involved in the development and progression of tumors. Let-7-related polymorphisms have been reported to be associated with tumorigenesis and prognosis. In gastric cancer, however, the related studies are limited. AIM: To investigate the role of let-7-related microRNA polymorphisms in the tumorigenesis and prognosis of gastric cancer in a Chinese population. METHODS: A total of 898 gastric cancer patients and 992 tumor-free controls were recruited into this study from 2008 to 2013. Gastric cancer patients were followed periodically. Ten single nucleotide polymorphisms (SNPs) in the let-7 gene region or their target mRNAs were genotyped using the MassARRAY system and their associations with the risk for or overall survival of gastric cancer were analyzed. RESULTS: All the ten SNPs were in Hardy-Weinberg equilibrium. The C allele of the rs3811463 polymorphism in the 3'-untranslated region (UTR) of LIN28A was associated with a lower risk of gastric cancer [odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.61-0.88, P = 0.001] after adjustment for age and Helicobacter pylori status. Seven hundred and thirty-five gastric cancer patients who had undergone radical tumorectomy were included in the survival analysis and their 5-year survival rate was 53.9% (95%CI: 50.1%-57.6%). The rs10889677 in the 3'-UTR of IL23R was corresponded to the prognosis of gastric cancer in a dose-response manner, in which the death risk increased by 25% [hazard ratio (HR) = 1.25, 95%CI: 1.04-1.45, P = 0.011] with each increase in the number of C alleles after controlling for other potential clinicopathological parameters. CONCLUSION: The let-7-related polymorphism rs3811463 in LIN28A is associated with the susceptibility to gastric cancer and the let-7-related polymorphism rs10889677 in IL23R is associated with the prognosis of gastric cancer.


Asunto(s)
Regulación Neoplásica de la Expresión Génica/genética , MicroARNs/metabolismo , Proteínas de Unión al ARN/genética , Receptores de Interleucina/genética , Neoplasias Gástricas/genética , Regiones no Traducidas 3'/genética , Anciano , Grupo de Ascendencia Continental Asiática/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Pronóstico , Neoplasias Gástricas/mortalidad , Análisis de Supervivencia
16.
Int J Mol Sci ; 20(5)2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30823645

RESUMEN

Maternal diet modifies epigenetic programming in offspring, a potentially critical factor in the immune dysregulation of modern societies. We previously found that prenatal fish oil supplementation affects neonatal T-cell histone acetylation of genes implicated in adaptive immunity including PRKCZ, IL13, and TBX21. In this study, we measured H3 and H4 histone acetylation levels by chromatin immunoprecipitation in 173 term placentas collected in the prospective birth cohort, ALADDIN, in which information on lifestyle and diet is thoroughly recorded. In anthroposophic families, regular olive oil usage during pregnancy was associated with increased H3 acetylation at FOXP3 (p = 0.004), IL10RA (p = 0.008), and IL7R (p = 0.007) promoters, which remained significant after adjustment by offspring gender. Furthermore, maternal fish consumption was associated with increased H4 acetylation at the CD14 gene in placentas of female offspring (p = 0.009). In conclusion, prenatal olive oil intake can affect placental histone acetylation in immune regulatory genes, confirming previously observed pro-acetylation effects of olive oil polyphenols. The association with fish consumption may implicate ω-3 polyunsaturated fatty acids present in fish oil. Altered histone acetylation in placentas from mothers who regularly include fish or olive oil in their diets could influence immune priming in the newborn.


Asunto(s)
Aceites de Pescado/farmacología , Histonas/metabolismo , Fenómenos Fisiologicos Nutricionales Maternos , Aceite de Oliva/farmacología , Placenta/metabolismo , Procesamiento Proteico-Postraduccional , Acetilación , Femenino , Aceites de Pescado/administración & dosificación , Aceites de Pescado/metabolismo , Productos Pesqueros , Humanos , Inmunidad Innata/genética , Interleucina-13/genética , Interleucina-13/metabolismo , Receptores de Lipopolisacáridos/genética , Receptores de Lipopolisacáridos/metabolismo , Aceite de Oliva/administración & dosificación , Placenta/efectos de los fármacos , Embarazo , Proteína Quinasa C/genética , Proteína Quinasa C/metabolismo , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo
17.
Biochem Biophys Res Commun ; 510(4): 515-519, 2019 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-30738578

RESUMEN

Glioblastoma (GBM) is one of the major cause of the cancer-related fatality worldwide. Several circular RNAs (circRNAs) have been observed to exert functions in GBM. The current study is aimed to explore the potential mechanism of circ_0074027 via miR-518a-5p and IL17RD in GBM progression. Circ_0074027 expression was determined in a cohort of 50 pairs of GBM specimens and five cell lines by qRT-PCR. In addition, the association between circ_0074027 expression and its clinical value was analyzed by Fisher's exact test. Cell growth, clone formation, apoptosis, migration and invasion was evaluated after overexpress or knockdown the expression of circ_0074027 in GBM cells. Dual luciferase reporter assays were conducted to evaluate the relevant intermolecular target relationships. Circ_0074027 expression was evidently upregulated in GBM tissue specimens and cells compared to the adjacent non-tumorous tissues and NHA, respectively. The upregulation of circ_0074027 is related to clinical severity and exerts oncogenic functions in GBM. Moreover, circ_0074027 could sponge miR-518a-5p to release its suppression on IL17RD. Our findings provide evidence that circ_0074027 plays an oncogenic role in GBM by regulating miR-518a-5p/IL17RD signaling.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , MicroARNs/genética , Receptores de Interleucina/genética , Adulto , Proliferación Celular , Progresión de la Enfermedad , Femenino , Glioblastoma/patología , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Regulación hacia Arriba
18.
Acta Derm Venereol ; 99(6): 579-586, 2019 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-30809683

RESUMEN

Prurigo nodularis is a highly pruritic and hyperplastic chronic dermatosis with unknown pathogenesis. Many pruritogenic mediators, including nerve growth factor, interleukin (IL)-31, thymic stromal lymphopoietin, and endothelin-1, are implicated in chronic itch and inflammation. This study investigated the mRNA levels and immunoreactivity of the nerve growth factor, IL-31, thymic stromal lymphopoietin, and endothelin axes in both lesional and perilesional skin in prurigo nodularis by using quantitative real-time PCR and immunohistochemistry studies. The nerve growth factor high-affinity receptor tyrosine kinase receptor A was upregulated while the low affinity receptor p75 neurotrophin receptor was downregulated in prurigo nodularis lesions. Downregulated expression of IL-31/IL-31 receptor A and endothelin-3/endothelin receptor B and upregulation of thymic stromal lymphopoietin receptor were found in prurigo nodularis lesions. Aberrant expression of nerve growth factor, IL-31, thymic stromal lymphopoietin and endothelin axes was found in prurigo nodularis lesions, especially in the epidermis, indicating the importance of keratinocytes in prurigo nodularis pathogenesis.


Asunto(s)
Epidermis/metabolismo , Queratinocitos/metabolismo , Prurigo/genética , Prurigo/metabolismo , Adulto , Citocinas/genética , Citocinas/metabolismo , Regulación hacia Abajo , Endotelina-3/genética , Endotelina-3/metabolismo , Femenino , Expresión Génica , Humanos , Hipersensibilidad/complicaciones , Hipersensibilidad/genética , Hipersensibilidad/metabolismo , Subunidad alfa del Receptor de Interleucina-7/genética , Subunidad alfa del Receptor de Interleucina-7/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Masculino , Persona de Mediana Edad , Factor de Crecimiento Nervioso/genética , Factor de Crecimiento Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Prurigo/complicaciones , ARN Mensajero/metabolismo , Receptor de Endotelina B/genética , Receptor de Endotelina B/metabolismo , Receptor trkA/genética , Receptor trkA/metabolismo , Receptores de Citocinas/genética , Receptores de Citocinas/metabolismo , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Receptores de Factor de Crecimiento Nervioso/genética , Receptores de Factor de Crecimiento Nervioso/metabolismo , Regulación hacia Arriba
19.
Z Rheumatol ; 78(3): 272-280, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29691688

RESUMEN

OBJECTIVE: The aim of this study was to determine whether interleukin-23R (IL-23R) polymorphisms are associated with susceptibility to ankylosing spondylitis (AS). METHODS: Meta-analyses were conducted to determine the associations between IL-23R polymorphisms and AS susceptibility in Europeans, Asians, and all subjects combined. RESULTS: A total of 17 studies (21 separate comparisons) were included in this meta-analysis. The meta-analysis revealed a significant association between AS and the two alleles of the rs11209032 polymorphism in all study subjects (odds ratio [OR] = 1.160, 95% confidence interval [CI] = 1.091-1.204, P < 0.001). Stratification by ethnicity identified a significant association between this polymorphism and AS in Europeans (OR = 1.234, 95% CI = 1.159-1.313, P < 0.001), but not in Asians (OR = 1.003, 95% CI = 0.920-1.219, P = 0.942). Meta-analyses of the rs1004819, rs10489629, rs1343151, rs1495965, rs7517847, and rs11465804 polymorphisms showed the same pattern as shown for rs11209032. The meta-analysis also revealed a significant association between the two alleles of the rs2201841 and rs11209026 polymorphisms and the risk of developing AS in Europeans, but not in Asians. Interestingly, the rs10889677 polymorphism was not found to be associated with AS susceptibility in either Europeans or Asians. CONCLUSIONS: This meta-analysis showed that several IL-23R polymorphisms are associated with the development of AS in Europeans.


Asunto(s)
Receptores de Interleucina/genética , Espondilitis Anquilosante , Grupo de Ascendencia Continental Asiática/genética , Grupo de Ascendencia Continental Europea/genética , Predisposición Genética a la Enfermedad , Humanos , Interleucinas , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Espondilitis Anquilosante/genética
20.
Genomics ; 111(4): 930-935, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-29864461

RESUMEN

In this study, we summarized the association of IL-23R gene polymorphisms with hepatocellular carcinoma (HCC). A total of 270 HCC patients were selected as HCC group, and 251 healthy individuals served as the control group. PCR-RFLP was performed to detect IL-23R gene polymorphism, including rs17375018 and rs11805303. Survival rate and risk factors of HCC were identified. The findings suggested that IL-23R rs17375018 was correlated with genetic susceptibility to HCC, and GC haplotype was closely linked with the risk factors of HCC. Moreover, rs17375018 polymorphism was related to portal vein tumor thrombus (PVTT) and alcohol consumption in HCC patients, while prognosis was better in HCC patients with AA genotype of rs17375018 polymorphism. Lastly, GG genotype in rs17375018, PVTT and TNM stage III and IV were identified as independent risk factors for HCC. In conclusion, IL-23R rs17375018 polymorphism might serve as a prognostic factor in patients with HCC after interventional therapy.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Polimorfismo de Nucleótido Simple , Receptores de Interleucina/genética , Adulto , Anciano , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Femenino , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad
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