Is there an Inflammation Role for MYD88 in Rheumatoid Arthritis?

Autor: Gomes da Silva IIF; Department of Genetics, Federal University of Pernambuco, Rua Prof Moraes Rego, 1235, Cidade Universitária, Recife, Pernambuco, 50670-901, Brazil. iisauragomes@gmail.com.; Laboratory of Immunopathology Keizo Asami, Recife, Pernambuco, Brazil. iisauragomes@gmail.com., Lima CAD; Laboratory of Immunopathology Keizo Asami, Recife, Pernambuco, Brazil.; Department of Oceanography, Federal University of Pernambuco, Recife, Pernambuco, Brazil., Silva JEA; Laboratory of Immunopathology Keizo Asami, Recife, Pernambuco, Brazil., Rushansky E; Division of Clinical Rheumatology, University of Pernambuco, Recife, PE, Brazil., Mariano MHQA; Division of Clinical Rheumatology, University of Pernambuco, Recife, PE, Brazil., Rolim P; Clinical Immunology Division, Department of Medicine, Medicine Faculty of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Oliveira RDR; Clinical Immunology Division, Department of Medicine, Medicine Faculty of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Louzada-Júnior P; Clinical Immunology Division, Department of Medicine, Medicine Faculty of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Souto FO; Laboratory of Immunopathology Keizo Asami, Recife, Pernambuco, Brazil.; Núcleo de Ciências da Vida, Centro Acadêmico do Agreste, Federal University of Pernambuco, Recife, Pernambuco, Brazil., Crovella S; Department of Genetics, Federal University of Pernambuco, Rua Prof Moraes Rego, 1235, Cidade Universitária, Recife, Pernambuco, 50670-901, Brazil.; Laboratory of Immunopathology Keizo Asami, Recife, Pernambuco, Brazil., de Azevêdo Silva J; Department of Genetics, Federal University of Pernambuco, Rua Prof Moraes Rego, 1235, Cidade Universitária, Recife, Pernambuco, 50670-901, Brazil.; Laboratory of Immunopathology Keizo Asami, Recife, Pernambuco, Brazil., Sandrin-Garcia P; Department of Genetics, Federal University of Pernambuco, Rua Prof Moraes Rego, 1235, Cidade Universitária, Recife, Pernambuco, 50670-901, Brazil.; Laboratory of Immunopathology Keizo Asami, Recife, Pernambuco, Brazil.
Jazyk: angličtina
Zdroj: Inflammation [Inflammation] 2021 Jun; Vol. 44 (3), pp. 1014-1022. Date of Electronic Publication: 2021 Jan 06.
DOI: 10.1007/s10753-020-01397-5
Abstrakt: 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: MEDLINE
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