Is there an Inflammation Role for MYD88 in Rheumatoid Arthritis?
| Autor: | Paulo Louzada-Junior, Fabrício Oliveira Souto, Isaura Isabelle Fonseca Gomes da Silva, Paula Sandrin-Garcia, Maria Helena Queiroz Araujo Mariano, Sergio Crovella, Renê Donizeti Ribeiro de Oliveira, José Eduardo Adelino Silva, Eliezer Rushansky, Jaqueline de Azevêdo Silva, Camilla Albertina Dantas de Lima, Patrícia Rolim |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Lipopolysaccharides Male medicine.medical_specialty Immunology Interleukin-1beta Polymorphism Single Nucleotide Arthritis Rheumatoid 03 medical and health sciences 0302 clinical medicine Immune system Polymorphism (computer science) Internal medicine Gene expression Genotype medicine Immunology and Allergy Humans Genetic Predisposition to Disease Allele Cells Cultured Genetic Association Studies business.industry Monocyte Middle Aged medicine.disease Rheumatology 030104 developmental biology medicine.anatomical_structure Phenotype 030220 oncology & carcinogenesis Rheumatoid arthritis Case-Control Studies Myeloid Differentiation Factor 88 Leukocytes Mononuclear Female business Brazil |
| Zdroj: | Inflammation. 44(3) |
| ISSN: | 1573-2576 |
| Popis: | Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease with strong genetic influence, especially upon immune response components. Several cytokines from the toll-like receptors activation pathway display recognized role for RA establishment. However, few studies have verified the role of key mediators such as MYD88 gene and its genetic variants. In the present study, we aim to evaluate the rs6853 functional single-nucleotide variation (SNV) role in RA etiopathogenesis, clinical severity status, and its impact in MYD88 mRNA levels and IL-lβ protein levels. For the association study, a total of 423 RA patients and 346 health individuals, enrolled as control, from Northeast and Southeast Brazil were genotyped using specific Taqman probe. For the gene expression assays, we performed a MYD88 rs6853 genotype-guided monocyte cell culture divided into non-stimulated and lypopolysaccharides (LPS)-stimulated cells from healthy individuals. MYD88 gene expression was measured using primer specifics while IL-1β levels were evaluated by ELISA. We observed that A allele and AA genotype were associated to an increased risk to RA development (OR = 1.60; 95% CI 1.24–2.08; p = 0.0004/OR = 2.83; 95% CI 1.25–6.41; p = 0.0152). The AA genotype exhibited lower MYD88 mRNA levels than GG genotype in non-stimulated monocyte cell culture (FC − 3.83; p = 0.003). Additionally, we verified an increase of IL-1β levels when AA genotype non-stimulated monocytes were compared to AA genotype LPS-stimulates (p = 0.021). In summary, MYD88 rs6853 polymorphism associated to RA development in our Brazilian cohort and showed influence upon MYD88 mRNA levels’ expression and IL-lβ production. |
| Databáze: | OpenAIRE |
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