N-acetyl-l-cysteine controls osteoclastogenesis through regulating Th17 differentiation and RANKL production in rheumatoid arthritis.

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.

CONCLUSION:

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.

• Authors: Hae-Rim Kim, Kyoung-Woon Kim, Bo-Mi Kim, Kyung-Ann Lee, Sang-Heon Lee
• Journal: The Korean journal of internal medicine (Korean J Intern Med) Vol. 34 Issue 1 Pg. 210-219 (01 2019) ISSN: 2005-6648 [Electronic] Korea (South)
• PMID: 28286938 (Publication Type: Journal Article)

Chemical References

• Interleukin-17
• RANK Ligand
• TNFSF11 protein, human
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Adult
• Aged
• Arthritis, Rheumatoid (drug therapy, immunology, pathology)
• Cell Differentiation (drug effects, immunology)
• Fibroblasts (drug effects, immunology, pathology)
• Humans
• In Vitro Techniques
• Interleukin-17 (metabolism)
• Middle Aged
• Osteogenesis (drug effects, immunology)
• RANK Ligand (genetics, metabolism)
• Signal Transduction (drug effects)
• Synovial Membrane (drug effects, immunology, pathology)
• Th17 Cells (drug effects, immunology, pathology)