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Elevated Interleukin-18 Receptor Accessory Protein Mediates Enhancement in Reactive Oxygen Species Production in Neutrophils of Systemic Lupus Erythematosus Patients.
Ma, Jie; Lam, Ian Kar Yin; Lau, Chak-Sing; Chan, Vera Sau Fong.
Afiliación
  • Ma J; Division of Rheumatology and Clinical Immunology, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
  • Lam IKY; Division of Rheumatology and Clinical Immunology, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
  • Lau CS; Division of Rheumatology and Clinical Immunology, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
  • Chan VSF; Division of Rheumatology and Clinical Immunology, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Cells ; 10(5)2021 04 21.
Article en En | MEDLINE | ID: mdl-33919154
Interleukin-18 receptor accessory protein (IL18RAP) is an indispensable subunit for the IL-18 receptor (IL-18R) complex's ability to mediate high-affinity IL-18 binding and signalling transduction. Interest in IL-18 in systemic lupus erythematosus (SLE) has been mostly focused on its role as a type 1 T helper cell-driving cytokine. The functional significance of IL18RAP in mediating the IL-18-driven response in myeloid cells in SLE remains largely unexplored. This study aimed to investigate the expression and function significance of IL18RAP in neutrophils of SLE patients. By qRT-PCR and Western blot analyses, elevated expressions of IL18RAP mRNA and protein were observed in neutrophils from SLE patients-particularly those with a history of nephritis. IL18RAP expression correlated negatively with complement 3 level and positively with disease activity, with higher expression in patients exhibiting renal and immunological manifestations. The increased IL18RAP expression in SLE neutrophils could be attributed to elevated type I interferon level in sera. Functionally, neutrophils from SLE patients showed higher IL-18-mediated enhancement in reactive oxygen species (ROS) generation, which showed positive correlation with IL18RAP expression and could be neutralized by anti-IL18RAP blocking antibodies. Taken together, our findings suggest that IL-18 could contribute to SLE pathogenesis through mediation of neutrophil dysfunction via the upregulation of IL18RAP expression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Especies Reactivas de Oxígeno / Subunidad beta del Receptor de Interleucina-18 / Lupus Eritematoso Sistémico / Neutrófilos Tipo de estudio: Observational_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Cells Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Especies Reactivas de Oxígeno / Subunidad beta del Receptor de Interleucina-18 / Lupus Eritematoso Sistémico / Neutrófilos Tipo de estudio: Observational_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Cells Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza