Retinoic Acid-Platinum (II) Complex [RT-Pt(II)] Protects Against Rheumatoid Arthritis in Mice via MEK/Nuclear Factor kappa B (NF-κB) Pathway Downregulation.

Abstract

BACKGROUND Rheumatoid arthritis (RA) is an inflammatory disorder that is present in approximately 1% of the world's population. This study was aimed to investigate the effect of retinoic acid-platinum (II) complex [RT-Pt(II)] on rheumatoid arthritis (RA) and to explore the mechanism involved. MATERIAL AND METHODS MH7A cell viability was determined by MTT assay and apoptosis was assessed using FACSCalibur flow cytometry. RT-PCR and Western blot assays were used for assessment of mRNA and proteins levels. RESULTS Treatment of rheumatoid arthritis with RT-Pt(II) significantly reduced the levels of IL‑1ß, IL-6, IL-8, MMP-1, and MMP-13 in synovial fluid of mice in a dose-dependent manner. The expression of iNOS and COX-2 mRNA and protein in rheumatoid arthritis rats was also significantly inhibited by treatment with RT-Pt(II). The TNF-alpha-induced proliferation of MH7A cells was alleviated by RT-Pt(II) treatment in a concentration-dependent manner. Moreover, RT-Pt(II) treatment induced apoptosis and caused arrest of cell cycle in MH7A cells. The activation of MEK/NF-kappaB pathway was downregulated by RT-Pt(II) treatment in MH7A cells. CONCLUSIONS In summary, the present study demonstrated that RT-Pt(II) inhibits TNF-alpha-induced inflammatory response, suppresses cell viability, and induces apoptosis in rheumatoid arthritis synovial cells. Moreover, RT-Pt(II) exhibited its effect through targeting the MEK/NF-kappaB pathway. Therefore, RT-Pt(II) can be used for the development of treatments for rheumatoid arthritis.

• Authors: Ziqiang Cui, Yaping Lin, Yuhong Liu, Ling Cao, Li Cui
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 26 Pg. e924787 (Aug 03 2020) ISSN: 1643-3750 [Electronic] United States
• PMID: 32741960 (Publication Type: Journal Article)

Chemical References

• Antirheumatic Agents
• Coordination Complexes
• IL1B protein, mouse
• Interleukin-1beta
• Interleukin-6
• Interleukin-8
• NF-kappa B
• Platinum Compounds
• Tumor Necrosis Factor-alpha
• interleukin-6, mouse
• Tretinoin
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Cyclooxygenase 2
• Ptgs2 protein, rat
• Mitogen-Activated Protein Kinase Kinases
• Matrix Metalloproteinase 13
• Mmp13 protein, mouse

Topics

• Animals
• Antirheumatic Agents (chemical synthesis, pharmacology)
• Apoptosis (drug effects, genetics)
• Arthritis, Rheumatoid (drug therapy, genetics, immunology, pathology)
• Cell Line
• Coordination Complexes (chemical synthesis, pharmacology)
• Cyclooxygenase 2 (genetics, immunology)
• Disease Models, Animal
• Gene Expression Regulation
• Humans
• Interleukin-1beta (genetics, immunology)
• Interleukin-6 (genetics, immunology)
• Interleukin-8 (genetics, immunology)
• Male
• Matrix Metalloproteinase 13 (genetics, immunology)
• Mice
• Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors, genetics, immunology)
• NF-kappa B (antagonists & inhibitors, genetics, immunology)
• Nitric Oxide Synthase Type II (genetics, immunology)
• Platinum Compounds (chemical synthesis, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction
• Synovial Fluid (cytology, immunology)
• Synoviocytes (drug effects, immunology, pathology)
• Tretinoin (chemistry)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, pharmacology)