Genomic Association between SNP Markers and Diseases in the "Curraleiro Pé-Duro" Cattle.

Susceptibility to diseases is inherited and can be transmitted between populations. Single-nucleotide polymorphism (SNPs) in genes related to immune response is associated with diseases in cattle. This study investigated SNPs in the genomic region of cytokines in 702 samples of Curraleiro Pé-Duro cattle and associated them with the occurrence of antibodies in brucellosis, leptospirosis, neosporosis, leukosis, infectious bovine rhinotracheitis (IBR), and bovine viral diarrhea (BVD) tests. DNA samples were evaluated by the kompetitive allele-specific polymerase chain reaction (KASP) method to identify polymorphisms. The gametic phase and SNP haplotypes were determined with the help of PHASE 2.1.1 software. Haplotypes were associated with serological results against Brucella abortus, Leptospira sp., Neospora caninum, leukosis, infectious rhinotracheitis, and BVD using univariate analysis followed by logistic regression. Haplotype 2 of TLR2 was present in 70% of the animals that tested positive for N. caninum infection. Haplotypes of TLR10 and TLR6 and IL10RA were more common in seronegative animals. Haplotypes related to the gene IL10RA were associated with animals negative to all infections. Curraleiro Pé-Duro cattle presented polymorphisms related to resistance to bacterial, viral, and N. caninum infections.

Polimorfismos del gen de interleucina 10 y respuesta virológica sostenida en pacientes cubanos coinfectados con virus de hepatitis C y virus de inmunodeficiencia humana / Interleukin-10 gene polymorphisms and sustained virological response in Cuban patients coinfected with hepatitis C virus and human immunodeficiency virus

Introducción: En pacientes infectados con el virus de la hepatitis C se demostró que los polimorfismos de un simple nucleótido del gen de la interleucina 10 (IL10), influyen en la respuesta virológica sostenida al tratamiento con interferón y ribavirina, y en la inmunopatogénesis de la enfermedad. Objetivo: Determinar la frecuencia de los polimorfismos de un simple nucleótido de la región promotora del gen de la interleucina 10, según respuesta virológica sostenida y grado de lesión hepática. Métodos: Se realizó un estudio descriptivo, de corte transversal y se determinó la carga del virus de la hepatitis C por RT-PCR en tiempo real. Se estudiaron 25 pacientes cubanos con virus de inmunodeficiencia humana coinfectados con VHC, 24 semanas después del tratamiento con interferón y ribavirina. Para evaluar la variabilidad genética de la interleucina 10, los polimorfismos de un simple nucleótido se identificaron por secuenciación nucleotídica, -592 (A>C) y -819 (T>C). El grado de fibrosis hepática se calculó por el índice aspartato aminotransferasa/plaquetas. Resultados: El 44,0 por ciento (11/25) de los pacientes lograron respuesta virológica sostenida, y en el 56,0 por ciento (14/25) restante no se obtuvo esta. En los individuos en que se dio la respuesta predominaron los genotipos bajos productores de la interleucina 10, -592AA (36,3 por ciento vs. 21,4 por ciento) y -819TT (54,5 por ciento vs. 21,4 por ciento). En estos casos, el análisis de la frecuencia alélica mostró mayor frecuencia del alelo T para el SNP -819 (p= 0,0470). El índice aspartato aminotransferasa/plaquetas fue compatible con fibrosis hepática sin cirrosis en pacientes sin respuesta virológica sostenida, mientras que en los coinfectados que tuvieron respuesta indicó ausencia de lesión hepática. Conclusiones: Los resultados sugieren que las variantes de los polimorfismos de un simple nucleótido del gen de la interleucina 10 evaluados, podrían estar relacionados con la respuesta virológica sostenida y la patogénesis de la hepatitis C en los pacientes estudiados(AU)

Introduction: The study of patients infected with hepatitis C virus revealed that polymorphisms of a single nucleotide of the interleukin-10 (IL10) gene influence the sustained virological response to the treatment with interferon and ribavirin, and the immunopathogenesis of the disease. Objective: Determine the frequency of single-nucleotide polymorphisms from the interleukin-10 gene promoter region according to the sustained virological response and the degree of liver injury. Methods: A descriptive cross-sectional study was conducted and hepatitis C viral load was determined by RT-PCR. A sample of 25 Cuban HIV/HCV coinfected patients were studied 24 weeks after treatment with interferon and ribavirin. To evaluate the genetic variability of interleukin 10, the single-nucleotide polymorphisms were identified by nucleotide sequencing, -592 (A>C) and -819 (T>C). The degree of liver fibrosis was estimated by the aspartate aminotransferase / platelet index. Results: Of the patients studied, 44.0 percent (11/25) achieved a sustained virological response and 56.0 percent (14/25) did not. In individuals displaying the response, a predominance was found of low interleukin-10 producing genotypes, -592AA (36.3 percent vs. 21.4 percent) and -819TT (54.5 percent vs. 21.4 percent). In those cases, allele frequency analysis showed a greater allele T frequency for SNP -819 (p= 0.0470). The aspartate aminotransferase / platelet index was compatible with kidney fibrosis without cirrhosis in patients without a sustained virological response, and indicated an absence of liver injury in coinfected patients displaying a response. Conclusions: Results suggest that the variants evaluated of single-nucleotide polymorphisms of the interleukin-10 gene could be related to the sustained virological response and the pathogenesis of hepatitis C in the patients studied(AU)

Expression of the interleukin-10 signaling pathway genes in individuals with Down syndrome and periodontitis.

BACKGROUND: Individuals with Down syndrome (DS) have a higher prevalence and severity of periodontal disease, which cannot be explained by poor oral hygiene alone and is related to changes in the immune response. The aim of this study is to evaluate whether DS was associated with differential modulation of expression of genes associated with proinflammatory and anti-inflammatory responses in periodontal disease. METHODS: A total of 51 individuals were evaluated: 19 individuals with DS and periodontal disease (group 1), 20 euploid individuals with periodontal disease (group 2; positive control), and 12 euploid individuals without periodontal disease (group 3; negative control). Clinical periodontal evaluation and gingival biopsies were performed. Quantitative reverse transcription-polymerase chain reaction was used to determine expression levels of interleukin-10 (IL-10), the receptors IL-10RA and IL-10RB, intracellular adhesion molecule 1 (ICAM-1), interferon-γ-inducible protein 10 (IP-10), and the signaling intermediates Janus kinase 1, signal transducer and activator of transcription 3 (STAT-3), and suppressor of cytokine signaling 3 (SOCS-3). RESULTS: Expression of IL10, SOCS3, IP10, and ICAM1 mRNA in DS patients was significantly lower compared to euploid individuals with periodontal disease, whereas IL-10RB and STAT-3 mRNA levels were higher in individuals with DS. CONCLUSION: Reduced expression of IL-10 coupled with a possible increase of STAT3 activation (increase of STAT3 and reduction of SOCS3 mRNA) indicates an important modulation of the immune response, with attenuation of anti-inflammatory and increase of proinflammatory mediators. This modulation may be related to the increased prevalence and severity of periodontitis in individuals with DS.

Crystal structure of a soluble decoy receptor IL-22BP bound to interleukin-22.

Interleukin-22 (IL-22) plays an important role in the regulation of immune and inflammatory responses in mammals. The IL-22 binding protein (IL-22BP), a soluble receptor that specifically binds IL-22, prevents the IL-22/interleukin-22 receptor 1 (IL-22R1)/interleukin-10 receptor 2 (IL-10R2) complex assembly and blocks IL-22 biological activity. Here we present the crystal structure of the IL-22/IL-22BP complex at 2.75 A resolution. The structure reveals IL-22BP residues critical for IL-22 binding, which were confirmed by site-directed mutagenesis and functional studies. Comparison of IL-22/IL-22BP and IL-22/IL-22R1 crystal structures shows that both receptors display an overlapping IL-22 binding surface, which is consistent with the inhibitory role played by IL-22 binding protein.