Expression of sterile-α and armadillo motif containing protein (SARM) in rheumatoid arthritis monocytes correlates with TLR2-induced IL-1ß and disease activity.
Rheumatology (Oxford)
; 60(12): 5843-5853, 2021 12 01.
Article
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| MEDLINE
| ID: mdl-33605409
ABSTRACT
OBJECTIVE:
Cartilage and bone damage in RA are associated with elevated IL-1ß. The effects of IL-1ß can be reduced by biological therapies that target IL-1ß or TNF-α. However, the mechanisms responsible for increased IL-1ß and the effect of anti-TNF-α have not been fully elucidated. Recently, sterile-α and armadillo motif containing protein (SARM) was identified as a negative regulator of toll-like receptor (TLR) induced IL-1ß secretion through an interaction with the inflammasome. This study set out to investigate SARM during TLR-induced IL-1ß secretion in RA peripheral blood monocytes and in patients commencing anti-TNF-α treatment.METHODS:
Monocytes were isolated from RA patients and healthy controls; disease activity was measured by DAS28. IL-1ß secretion was measured by ELISA following TLR1/2, TLR4 and TLR7/8 stimulation. The mRNA expression of SARM1, IL-1ß and the components of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome were measured by quantitative PCR. SARM protein expression was measured by western blotting.RESULTS:
TLR1/2 activation induced elevated IL-1ß in RA monocytes compared with healthy controls (P = 0.0009), which negatively correlated with SARM1 expression (P = 0.0086). Lower SARM expression also correlated with higher disease activity (P = 0.0246). Additionally, patients responding to anti-TNF-α treatment demonstrated a rapid upregulation of SARM, which was not observed in non-responders.CONCLUSION:
Together, these data highlight a potential contribution from SARM to RA pathophysiology where decreased SARM may lead to elevated IL-1ß associated with RA pathogenesis. Furthermore, the data additionally present a potential mechanism by which TNF-α blockade can modify IL-1ß secretion.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Artritis Reumatoide
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ARN
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Regulación de la Expresión Génica
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Proteínas del Citoesqueleto
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Proteínas del Dominio Armadillo
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Receptor Toll-Like 2
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Interleucina-1beta
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Inflamasomas
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Adult
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Female
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Humans
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Male
Idioma:
En
Año:
2021
Tipo del documento:
Article