N-acetyl-l-cysteine controls osteoclastogenesis through regulating Th17 differentiation and RANKL in rheumatoid arthritis.
- Author:
Hae Rim KIM
1
;
Kyoung Woon KIM
;
Bo Mi KIM
;
Kyung Ann LEE
;
Sang Heon LEE
Author Information
- Publication Type:Original Article
- Keywords: Acetylcysteine; Arthritis, rheumatoid; Osteogenesis; RANK ligand; Interleukin-17
- MeSH: Acetylcysteine*; Arthritis, Rheumatoid*; Coculture Techniques; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Flow Cytometry; Humans; Interferons; Interleukin-17; Interleukin-2; Interleukin-4; JNK Mitogen-Activated Protein Kinases; Macrophage Colony-Stimulating Factor; Monocytes; Osteoclasts; Osteogenesis; Phosphorylation; RANK Ligand; Real-Time Polymerase Chain Reaction; Sirolimus; T-Lymphocytes; Th17 Cells
- From:The Korean Journal of Internal Medicine 2019;34(1):210-219
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND/AIMS: This study aimed to determine the regulatory role of N-acetyl-l-cysteine (NAC), an antioxidant, in interleukin 17 (IL-17)-induced osteoclast differentiation in rheumatoid arthritis (RA). METHODS: After RA synovial fibroblasts were stimulated by IL-17, the expression and production of receptor activator of nuclear factor κ-B ligand (RANKL) was determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis was also determined after co-cultures of IL-17-stimulated RA synovial fibroblasts, Th17 cells and various concentrations of NAC with monocytes. After human peripheral CD4⁺ T cells were cultured with NAC under Th17 condition, IL-17, interferon γ, IL-4, Foxp3, RANKL, and IL-2 expression and production was determined by flow cytometry or ELISA. RESULTS: When RA synovial fibroblasts were stimulated by IL-17, IL-17 stimulated the production of RANKL, and NAC reduced the IL-17-induced RANKL production in a dose-dependent manner. NAC decreased IL-17-activated phosphorylation of mammalian target of rapamycin, c-Jun N-terminal kinase, and inhibitor of κB. When human peripheral blood CD14⁺ monocytes were cultured with macrophage colony-stimulating factor and IL-17 or RANKL, osteoclasts were differentiated, and NAC reduced the osteoclastogenesis. After human peripheral CD4⁺ T cells were co-cultured with IL-17-pretreated RA synovial fibroblasts or Th17 cells, NAC reduced their osteoclastogenesis. Under Th17 polarizing condition, NAC decreased Th17 cell differentiation and IL-17 and RANKL production. CONCLUSIONS: NAC inhibits the IL-17-induced RANKL production in RA synovial fibroblasts and IL-17-induced osteoclast differentiation. NAC also reduced Th17 polarization. NAC could be a supplementary therapeutic option for inflammatory and bony destructive processes in RA.
