Elevated Interleukin-18 Receptor Accessory Protein Mediates Enhancement in Reactive Oxygen Species Production in Neutrophils of Systemic Lupus Erythematosus Patients
| Autor: | Chak Sing Lau, Ian Kar Yin Lam, Jie Ma, Vera S. F. Chan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine interleukin-18 receptor accessory protein Neutrophils QH301-705.5 medicine.medical_treatment SLE Article Pathogenesis 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Western blot Interferon Blocking antibody Humans Lupus Erythematosus Systemic Medicine Interleukin-18 Receptor beta Subunit Biology (General) Receptor 030203 arthritis & rheumatology medicine.diagnostic_test business.industry Interleukin-18 General Medicine Middle Aged Interleukin-18 receptor 030104 developmental biology Cytokine Case-Control Studies Interferon Type I Immunology type I interferon Female Reactive Oxygen Species business cellular function medicine.drug |
| Zdroj: | Cells Volume 10 Issue 5 Cells, Vol 10, Iss 964, p 964 (2021) |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells10050964 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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