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1.
Laeknabladid ; 107(2): 63, 2021 02.
Artículo en Is | MEDLINE | ID: mdl-33501918
2.
Ann Rheum Dis ; 71(5): 707-9, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22219137

RESUMEN

BACKGROUND: The susceptibility to rheumatoid arthritis (RA) is partly heritable, but whether the severity of RA is also influenced by genetics has not been determined. The evaluation of the heritability of the severity of RA is basic to further studies on genetic factors. A study was undertaken to determine whether joint destruction is heritable. METHODS: Iceland has an unique comprehensive genealogy database covering today's population and stretching back to ≥1000 years ago, as well as genome-wide single nucleotide polymorphism data for a large part of the population. Hand and feet x-rays of 325 Icelandic patients with RA were scored according to the Sharp-van der Heijde method. The degree of relatedness between patients was estimated in two ways: (1) kinship coefficients (KC) on the genealogical data were expressed; and (2) the identical-by-descent (IBD) was estimated applying long-range phasing of the genetic profile of the patients. The degree of relatedness was tested against the similarity in joint destruction rates by linear regression analysis and the heritability of joint destruction was calculated. RESULTS: Significant associations between degree of relatedness and similarity in joint destruction rates were observed for both methods of determining relatedness (p(KC)=0.018, p(IBD)=0.003). The estimated heritability was 45% using KC and 58% using the estimated IBD data. CONCLUSIONS: The severity of joint destruction in RA is influenced by genetic factors.


Asunto(s)
Artritis Reumatoide , Predisposición Genética a la Enfermedad , Articulaciones/patología , Vigilancia de la Población , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/genética , Artritis Reumatoide/fisiopatología , Consanguinidad , Bases de Datos Factuales , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Articulaciones/fisiopatología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple
3.
Nat Commun ; 13(1): 1598, 2022 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-35332129

RESUMEN

Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and has a largely unknown underlying biology. In a genome-wide association study of CTS (48,843 cases and 1,190,837 controls), we found 53 sequence variants at 50 loci associated with the syndrome. The most significant association is with a missense variant (p.Glu366Lys) in SERPINA1 that protects against CTS (P = 2.9 × 10-24, OR = 0.76). Through various functional analyses, we conclude that at least 22 genes mediate CTS risk and highlight the role of 19 CTS variants in the biology of the extracellular matrix. We show that the genetic component to the risk is higher in bilateral/recurrent/persistent cases than nonrecurrent/nonpersistent cases. Anthropometric traits including height and BMI are genetically correlated with CTS, in addition to early hormonal-replacement therapy, osteoarthritis, and restlessness. Our findings suggest that the components of the extracellular matrix play a key role in the pathogenesis of CTS.


Asunto(s)
Síndrome del Túnel Carpiano , Antropometría , Síndrome del Túnel Carpiano/genética , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Fenotipo
4.
Nat Commun ; 13(1): 634, 2022 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-35110524

RESUMEN

Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (ORIDD = 0.92, P = 1.6 × 10-39; ORdorsalgia = 0.92, P = 7.2 × 10-15) is with a 3'UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 - 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10-11); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes.


Asunto(s)
Degeneración del Disco Intervertebral/genética , Desplazamiento del Disco Intervertebral/genética , Disco Intervertebral/metabolismo , Cotransportador de Sodio-Sulfato/genética , Cotransportador de Sodio-Sulfato/metabolismo , Sulfatos/metabolismo , Regiones no Traducidas 3' , Huesos/metabolismo , Estudio de Asociación del Genoma Completo , Humanos , Simportadores/genética , Simportadores/metabolismo
5.
Sci Rep ; 11(1): 4188, 2021 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-33602968

RESUMEN

Bell's palsy is the most common cause of unilateral facial paralysis and is defined as an idiopathic and acute inability to control movements of the facial muscles on the affected side. While the pathogenesis remains unknown, previous studies have implicated post-viral inflammation and resulting compression of the facial nerve. Reported heritability estimates of 4-14% suggest a genetic component in the etiology and an autosomal dominant inheritance has been proposed. Here, we report findings from a meta-analysis of genome-wide association studies uncovering the first unequivocal association with Bell's palsy (rs9357446-A; P = 6.79 × 10-23, OR = 1.23; Ncases = 4714, Ncontrols = 1,011,520). The variant also confers risk of intervertebral disc disorders (P = 2.99 × 10-11, OR = 1.04) suggesting a common pathogenesis in part or a true pleiotropy.


Asunto(s)
Parálisis de Bell/genética , Adulto , Anciano , Músculos Faciales/patología , Nervio Facial/patología , Parálisis Facial/genética , Femenino , Estudio de Asociación del Genoma Completo/métodos , Humanos , Inflamación/genética , Masculino , Persona de Mediana Edad , Movimiento/fisiología , Estudios Prospectivos , Riesgo
6.
Cancer Epidemiol Biomarkers Prev ; 29(1): 225-235, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31666285

RESUMEN

BACKGROUND: Alpha-fetoprotein (AFP), cancer antigens 15.3, 19.9, and 125, carcinoembryonic antigen, and alkaline phosphatase (ALP) are widely measured in attempts to detect cancer and to monitor treatment response. However, due to lack of sensitivity and specificity, their utility is debated. The serum levels of these markers are affected by a number of nonmalignant factors, including genotype. Thus, it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. METHODS: We performed genome-wide association studies of serum levels of AFP (N = 22,686), carcinoembryonic antigen (N = 22,309), cancer antigens 15.3 (N = 7,107), 19.9 (N = 9,945), and 125 (N = 9,824), and ALP (N = 162,774). We also examined the correlations between levels of these biomarkers and the presence of cancer, using data from a nationwide cancer registry. RESULTS: We report a total of 84 associations of 79 sequence variants with levels of the six biomarkers, explaining between 2.3% and 42.3% of the phenotypic variance. Among the 79 variants, 22 are cis (in- or near the gene encoding the biomarker), 18 have minor allele frequency less than 1%, 31 are coding variants, and 7 are associated with gene expression in whole blood. We also find multiple conditions associated with higher biomarker levels. CONCLUSIONS: Our results provide insights into the genetic contribution to diversity in concentration of tumor biomarkers in blood. IMPACT: Genetic correction of biomarker values could improve prediction algorithms and decision-making based on these biomarkers.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Niño , Preescolar , Femenino , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Humanos , Islandia/epidemiología , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/diagnóstico , Neoplasias/genética , Polimorfismo de Nucleótido Simple , Valor Predictivo de las Pruebas , Valores de Referencia , Sistema de Registros/estadística & datos numéricos , Análisis de Secuencia de ARN , Secuenciación Completa del Genoma , Adulto Joven
7.
Nat Commun ; 10(1): 1777, 2019 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-30992453

RESUMEN

Nerve conduction (NC) studies generate measures of peripheral nerve function that can reveal underlying pathology due to axonal loss, demyelination or both. We perform a genome-wide association study of sural NC amplitude and velocity in 7045 Icelanders and find a low-frequency splice-donor variant in PRPH (c.996+1G>A; MAF = 1.32%) associating with decreased NC amplitude but not velocity. PRPH encodes peripherin, an intermediate filament (IF) protein involved in cytoskeletal development and maintenance of neurons. Through RNA and protein studies, we show that the variant leads to loss-of-function (LoF), as when over-expressed in a cell line devoid of other IFs, it does not allow formation of the normal filamentous structure of peripherin, yielding instead punctate protein inclusions. Recall of carriers for neurological assessment confirms that from an early age, homozygotes have significantly lower sural NC amplitude than non-carriers and are at risk of a mild, early-onset, sensory-negative, axonal polyneuropathy.


Asunto(s)
Conducción Nerviosa/genética , Periferinas/genética , Polineuropatías/genética , Sitios de Empalme de ARN/genética , Nervio Sural/fisiopatología , Adulto , Edad de Inicio , Anciano , Axones/patología , Estudios de Casos y Controles , Línea Celular , Femenino , Estudios de Seguimiento , Estudio de Asociación del Genoma Completo , Homocigoto , Humanos , Islandia/epidemiología , Mutación con Pérdida de Función , Masculino , Persona de Mediana Edad , Polineuropatías/epidemiología , Polineuropatías/fisiopatología , Prevalencia , Empalme del ARN/fisiología
8.
Nat Commun ; 8: 14265, 2017 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-28223688

RESUMEN

Lumbar disc herniation (LDH) is common and often debilitating. Microdiscectomy of herniated lumbar discs (LDHsurg) is performed on the most severe cases to resolve the resulting sciatica. Here we perform a genome-wide association study on 4,748 LDHsurg cases and 282,590 population controls and discover 37 highly correlated markers associating with LDHsurg at 8q24.21 (between CCDC26 and GSDMC), represented by rs6651255[C] (OR=0.81; P=5.6 × 10-12) with a stronger effect among younger patients than older. As rs6651255[C] also associates with height, we performed a Mendelian randomization analysis using height polygenic risk scores as instruments to estimate the effect of height on LDHsurg risk, and found that the marker's association with LDHsurg is much greater than predicted by its effect on height. In light of presented findings, we speculate that the effect of rs6651255 on LDHsurg is driven by susceptibility to developing severe and persistent sciatica upon LDH.


Asunto(s)
Cromosomas Humanos Par 8/genética , Predisposición Genética a la Enfermedad , Variación Genética , Degeneración del Disco Intervertebral/genética , Desplazamiento del Disco Intervertebral/genética , Vértebras Lumbares/patología , Ciática/genética , Adulto , Secuencia de Bases , Estatura/genética , Demografía , Femenino , Sitios Genéticos , Humanos , Degeneración del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/cirugía , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo
10.
Carbohydr Polym ; 143: 131-8, 2016 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-27083352

RESUMEN

Achillea millefolium has been used in traditional medicine for a number of ailments, including skin inflammation and wounds. A polysaccharide fraction (Am-25-d) isolated from aqueous extract from A. millefolium had an average molecular weight of 270 kDa and a monosaccharide composition of GalA, Gal, Ara, Xyl, Rha in molar ratio of 28:26:23:9:7. THP-1 cells primed with IFN-γ and stimulated with LPS in the presence of Am-25-d secreted more IL-1ß, IL-8, IL-10, IL-12p40, IL-23 and TNF-α than THP-1 cells stimulated in the absence of Am-25-d. However, when added to unstimulated cells Am-25-d did not increase secretion of the cytokines examined. Stimulating THP-1 monocytes in the presence of Am-25-d led to decreased nuclear concentrations of NF-κB and phosphorylation of ERK1/2 and Akt kinases compared with that when the cells were stimulated without Am-25-d. These findings indicate that Am-25-d isolated from A. millefolium has immunoenhancing properties that may be mediated via the Akt pathway.


Asunto(s)
Achillea/química , Citocinas/metabolismo , Factores Inmunológicos/farmacología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , FN-kappa B/metabolismo , Polisacáridos/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , Humanos , Factores Inmunológicos/química , Factores Inmunológicos/aislamiento & purificación , Interleucina-10/metabolismo , Subunidad p40 de la Interleucina-12/metabolismo , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo
11.
J Immunol Methods ; 415: 36-45, 2014 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-25268546

RESUMEN

Murine zymosan-induced peritonitis is the model most frequently used to study resolution of inflammation. However, the antigen-induced peritonitis model may be better suited for studying resolution of inflammation and the adaptive phase that follows. The objective of this study was to provide an evaluation of the kinetics of cells and mediators during induction, resolution and the adaptive immune phases of a murine antigen-induced inflammation. Female C57BL/6 mice were immunized twice subcutaneously with mBSA and three weeks after the initial immunization they were injected intraperitoneally (i.p.) with mBSA, which induced peritonitis. Peritoneal cells were counted and expression of surface molecules and chemokine receptors analyzed with flow cytometry. Chemokine and cytokine concentrations in peritoneal fluid were determined by ELISA. Two neutrophil populations, differing in size and granularity and slightly in expression of surface molecules, were observed in the peritoneal cavity after induction of inflammation. Macrophages disappeared from the peritoneal cavity following i.p. administration of mBSA but appeared again as they differentiated from recruited monocytes and peaked in numbers at 48 h. At that time point, two distinct populations of macrophages were present in the peritoneal cavity; one with high expression of F4/80, also expressing the atypical chemokine receptor D6 as well as CCR7; the other expressing low levels of F4/80 and also expressing CD11c and CD138. Eosinophils appeared in the peritoneum 3h following i.p. administration of mBSA and peaked at 48 h. At that time point they had upregulated their expression of CCR3 but decreased their expression of CD11b. Peritoneal levels of CCL11 peaked at 6h and may have led to recruitment of the eosinophils. NK cells and T cells peaked at 48 h, whereas B cells peaked at 5 days, with the majority being B1 cells. Peritoneal concentrations of pro-inflammatory cytokines (IL-ß and IL-6) and chemokines (CCL2 and CCL3) peaked at 3h, whereas IL-1ra peaked at 6h, sTNF-R at 24h and sIL-6R and TGF-ß at 48 h. The results show kinetic alterations in cell populations and mediators in a murine model that may be an excellent model to study initiation and resolution of inflammation and the following adaptive phase.


Asunto(s)
Citocinas/biosíntesis , Macrófagos Peritoneales/inmunología , Neutrófilos/inmunología , Peritonitis/inmunología , Animales , Antígenos de Diferenciación/genética , Antígenos de Diferenciación/inmunología , Linfocitos B/inmunología , Linfocitos B/patología , Antígeno CD11c/genética , Antígeno CD11c/inmunología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Eosinófilos/inmunología , Eosinófilos/patología , Femenino , Expresión Génica , Inyecciones Intraperitoneales , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/patología , Macrófagos Peritoneales/patología , Ratones , Ratones Endogámicos C57BL , Neutrófilos/patología , Cavidad Peritoneal/patología , Peritonitis/inducido químicamente , Peritonitis/genética , Peritonitis/patología , Receptores CCR3/genética , Receptores CCR3/inmunología , Albúmina Sérica Bovina , Sindecano-1/genética , Sindecano-1/inmunología , Linfocitos T/inmunología , Linfocitos T/patología
12.
J Nutr Biochem ; 25(2): 111-7, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24332949

RESUMEN

The effects of omega-3 fatty acids on the adaptive immune response have mainly been analysed in vitro with varying results. How omega-3 fatty acids affect the adaptive immune response in vivo is largely unknown. This study examined the effects of dietary fish oil on the adaptive immune response in antigen-induced inflammation in mice, focusing on its effects on B cells and B cell subsets. Mice were fed a control diet with or without 2.8% fish oil, immunized twice with methylated BSA (mBSA) and peritonitis induced by intraperitoneal injection of mBSA. Serum, spleen and peritoneal exudate were collected prior to and at different time points after induction of peritonitis. Serum levels of mBSA-specific antibodies were determined by ELISA and the number of peritoneal and splenic lymphocytes by flow cytometry. The levels of germinal center B cells and IgM(+), IgG(+) and CD138(+) cells in spleen were evaluated by immunoenzyme staining. Mice fed the fish oil diet had more peritoneal B1 cells, more IgM(+) cells in spleen and higher levels of serum mBSA-specific IgM antibodies compared with that in mice fed the control diet. However, dietary fish oil did not affect the number of peritoneal B2 cells, splenic IgG(+) or CD138(+) cells or serum levels of mBSA-specific IgG antibodies in mice with mBSA-induced peritonitis. These results indicate that dietary fish oil can enhance the adaptive immune response, specifically the B1 cell response, which may lead to better protection against secondary infection as well as improvement in reaching homeostasis following antigenic challenge.


Asunto(s)
Antígenos/inmunología , Linfocitos B/inmunología , Ácidos Grasos Omega-3/farmacología , Peritonitis/inmunología , Animales , Femenino , Citometría de Flujo , Ratones , Ratones Endogámicos C57BL
13.
Phytomedicine ; 21(11): 1451-7, 2014 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-24877713

RESUMEN

Cyanobacteria (blue-green algae) have been consumed as food and used in folk medicine since ancient times to alleviate a variety of diseases. Cyanobacteria of the genus Nostoc have been shown to produce complex exopolysaccharides with antioxidant and antiviral activity. Furthermore, Nostoc sp. are common in cyanolichen symbiosis and lichen polysaccharides are known to have immunomodulating effects. Nc-5-s is a heteroglycan isolated from free-living colonies of Nostoc commune and its structure has been characterized in detail. The aim of this study was to determine the effects of Nc-5-s on the inflammatory response of lipopolysaccharide (LPS)-stimulated human THP-1 monocytes and how the effects are mediated. THP-1 monocytes primed with interferon-γ and stimulated with LPS in the presence of Nc-5-s secreted less of the pro-inflammatory cytokine interleukin (IL)-6 and more of the anti-inflammatory cytokine IL-10 than THP-1 monocytes stimulated without Nc-5-s. In contrast, Nc-5-s increased LPS-induced secretion of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α and IL-8. Nc-5-s decreased LPS-induced phosphorylation of the extracellular regulated kinase (ERK)1/2 and Akt kinase, but did not affect phosphorylation of the p38 kinase, activation of the nuclear factor kappa B pathway, nor DNA binding of c-fos. These results show that Nc-5-s has anti-inflammatory effects on IL-6 and IL-10 secretion by THP-1 monocytes, but its effects are pro-inflammatory when it comes to TNF-α and IL-8. Furthermore, they show that the effects of Nc-5-s may be mediated through the ERK1/2 pathway and/or the Akt/phosphoinositide 3-kinase pathway and their downstream effectors. The ability of Nc-5-s to decrease IL-6 secretion, increase IL-10 secretion and moderate ERK1/2 activation indicates a potential for its development as an anti-inflammatory agent.


Asunto(s)
Antiinflamatorios/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Monocitos/efectos de los fármacos , Nostoc commune/química , Polisacáridos/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipopolisacáridos , Fosforilación , Factor de Necrosis Tumoral alfa/metabolismo
14.
J Nutr Biochem ; 24(10): 1758-65, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23769761

RESUMEN

Dietary n-3 polyunsaturated fatty acids (PUFA) influence the inductive phase of inflammation but less is known about their effects on the resolution phase. This study examined the effects of dietary fish oil on induction and resolution of antigen-induced inflammation in mice. Mice were fed a control diet with or without 2.8% fish oil, immunized twice with methylated BSA (mBSA) and inflammation induced by intraperitoneal injection of mBSA. Prior to and at different time points after mBSA administration, peritoneal cells were analyzed and expression of surface molecules determined by flow cytometry. Concentration of chemokines, cytokines and soluble cytokine receptors was determined by ELISA. Mice fed the fish oil diet had fewer peritoneal neutrophils, shorter resolution interval and lower levels of pro-inflammatory cytokines and chemokines than mice fed the control diet. In mice fed the fish oil diet there was an early peak in peritoneal levels of the immunosuppressive molecules sIL-6R and TGF-ß, that was not seen in mice fed the control diet. In the resolution phase, peritoneal macrophages from mice fed the fish oil diet expressed more of the atypical chemokine receptor D6 and peritoneal TGF-ß levels were higher than that in mice fed the control diet. Furthermore, in the late-resolution phase there were more peritoneal eosinophils and macrophages in mice fed the fish oil diet than in mice fed the control diet. These results demonstrate a suppressive effect of n-3 PUFA on the inductive phase of inflammation and indicate an enhancing effect of n-3 PUFA on resolution of inflammation.


Asunto(s)
Grasas Insaturadas en la Dieta/uso terapéutico , Ácidos Grasos Omega-3/uso terapéutico , Aceites de Pescado/uso terapéutico , Peritonitis/prevención & control , Animales , Quimiocina CCL11/efectos de los fármacos , Quimiocina CXCL1/efectos de los fármacos , Femenino , Factor Estimulante de Colonias de Granulocitos/efectos de los fármacos , Inflamación/prevención & control , Interleucina-6/metabolismo , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Ratones , Ratones Endogámicos C57BL , Peritonitis/dietoterapia , Peritonitis/inmunología , Receptores de Interleucina-6/efectos de los fármacos , Albúmina Sérica Bovina/inmunología , Factor de Crecimiento Transformador beta/efectos de los fármacos
15.
J Ethnopharmacol ; 136(1): 88-93, 2011 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-21511021

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Menyanthes trifoliate and Achillea millefolium have been used in traditional medicine to ameliorate chronic inflammatory conditions. The aim of this study was to identify the effects of ethanol and aqueous extracts of Menyanthes trifoliate and Achillea millefolium on maturation of dendritic cells (DCs) and their ability to activate allogeneic CD4(+) T cells. MATERIALS AND METHODS: Human monocyte-derived DCs were matured in the absence or presence of lyophilised aqoueous or ethanol extracts from Menyanthes trifoliate or Achillea millefolium and their expression of surface molecules analysed with flow cytometry and cytokine secretion measured by ELISA. DCs matured in the presence of aqueous extracts from Menyanthes trifoliate and Achillea millefolium were co-cultured with allogeneic CD4(+) T cells and the expression of surface molecules by T cells and their cytokine secretion and cell proliferation determined. RESULTS: Maturation of DCs in the presence of aqueous extracts from Menyanthes trifoliate or Achillea millefolium did not affect expression of the surface molecules examined but reduced the ratio of secreted IL-12p40/IL-10, compared with that by DCs matured in the absence of extracts. Allogeneic CD4(+) T cells co-cultured with DCs matured in the presence of aqueous extract from Menyanthes trifoliate secreted less IFN-γ, IL-10 and IL-17 than CD4(+) T cells co-cultured with DCs matured without an extract. Maturation of DCs in the presence of aqueous extract from Achillea millefolium decreased IL-17 secretion but did not affect IFN-γ and IL-10 secretion by allogeneic CD4(+) T cells. CONCLUSIONS: Aqueous extract from Menyanthes trifoliate induces a suppressive phenotype of DCs that has reduced capacity to induce Th1 and Th17 stimulation of allogeneic CD4(+) T cells, whereas aqueous extract from Achillea millefolium reduces the capacity of DCs to induce a Th17 response.


Asunto(s)
Achillea , Linfocitos T CD4-Positivos/metabolismo , Células Dendríticas/efectos de los fármacos , Interleucinas/metabolismo , Activación de Linfocitos/efectos de los fármacos , Extractos Vegetales/farmacología , Diferenciación Celular/efectos de los fármacos , Células Dendríticas/citología , Células Dendríticas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Humanos
16.
Immunol Lett ; 136(1): 90-6, 2011 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-21237202

RESUMEN

Extracts and fractions from birch bark have been used to treat various diseases, such as skin disorders and rheumatism, and for analgesic effects. Results from studies in vitro and in vivo have shown that birch bark extracts can have immunoregulatory effects. These effects have mainly been attributed to the various triterpenes found in birch bark. The effects of birch bark from Betula pubescens on immune responses have not been reported. Ethanol extract was prepared from dry birch bark (DBBEE) and five fractions made using various ratios of dichloromethane and methanol (fractions I-V). Human monocyte-derived dendritic cells (DCs) were matured with or without DBBEE or fractions I-V at several concentrations. The effects of the extract and fractions on DC maturation were determined by measuring cytokine secretion by ELISA and expression of surface molecules by flow cytometry. DBBEE and fractions III and IV reduced DC secretion of IL-6, IL-10 and IL-12p40 and expression of CD83, CD86, CCR7 and DC-SIGN compared with control DCs. Proliferation of allogeneic CD4(+) T cells co-cultured with DCs matured with fraction IV, as measured by (3)H-thymidine incorporation, was similar to proliferation of allogeneic CD4(+) T cells co-cultured with control DCs. However, IFN-γ secretion was reduced and IL-10 and IL-17 secretion was increased, a cytokine profile consistent with a Th17 regulatory phenotype. These results indicate that bark from Betula pubescens contains compound(s) that can modulate DCs so that their interaction with T cells leads to an immunoregulatory response.


Asunto(s)
Betula/química , Betula/inmunología , Células Dendríticas/inmunología , Extractos Vegetales/farmacología , Células TH1/inmunología , Células Th17/inmunología , Técnicas de Cocultivo , Citocinas/inmunología , Citocinas/metabolismo , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Etanol/química , Humanos , Extractos Vegetales/química , Células TH1/efectos de los fármacos , Células Th17/efectos de los fármacos
17.
J Clin Immunol ; 27(3): 284-93, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17356923

RESUMEN

Mucosal tolerance has been shown to reduce disease severity in animal models mimicking human autoimmune diseases. The objective of this study was to examine whether mucosal tolerance against keyhole limpet haemocyanin (KLH) could be used to reduce bovine serum albumin (BSA)-induced arthritis in rats and whether anti-inflammatory drugs or passive cigarette smoke affected tolerance induction. Arthritis was induced by immunizing rats with BSA and then injecting BSA into one knee and saline into the other knee for comparison. Prior to BSA immunization, the rats were treated intranasally with KLH or saline and KLH then injected in the knee joints at the time of BSA injection, or the rats were treated with or without anti-inflammatory drugs or subjected to cigarette smoke prior to and during intranasal treatment with BSA. The rats that received intranasal treatment with KLH had a significantly less inflammation in their left knee joint compared to rats that received intranasal saline treatment. Beclamethasone increased the tolerance effect of BSA, whereas passive cigarette smoke abrogated the mucosal tolerance. This data suggests that bystander suppression can be used to treat arthritis and other autoimmune diseases, even when the autoantigen is not known.


Asunto(s)
Artritis/inmunología , Artritis/patología , Efecto Espectador/inmunología , Hemocianinas/inmunología , Tolerancia Inmunológica/inmunología , Albúmina Sérica Bovina/inmunología , Animales , Artritis/inducido químicamente , Artritis/tratamiento farmacológico , Beclometasona/uso terapéutico , Efecto Espectador/efectos de los fármacos , Bovinos , Proliferación Celular/efectos de los fármacos , Femenino , Tolerancia Inmunológica/efectos de los fármacos , Inmunidad Mucosa/efectos de los fármacos , Inmunidad Mucosa/inmunología , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Ratas , Receptores del Factor de Necrosis Tumoral/metabolismo , Albúmina Sérica Bovina/toxicidad , Bazo/citología , Bazo/efectos de los fármacos , Bazo/metabolismo , Contaminación por Humo de Tabaco/efectos adversos
18.
Postgrad Med ; 94(8): 165-180, 1993 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29206547

RESUMEN

Preview Once considered relatively benign, rheumatoid arthritis is now recognized as a disabling systemic disease that causes substantial morbidity and mortality. Early, aggressive therapy may be critical for altering the course of disease. Drs Vikings-son and Graziano describe the causes and clinical course of rheumatoid arthritis and discuss diagnostic considerations and prognostic indicators that support optimum management.

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