A systematic review and meta-analysis: effects of glucocorticoids on rheumatoid arthritis and systemic lupus erythematosus.

BACKGROUND: Meta-analysis was performed to explore the efficacy of glucocorticoids in the treatment of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), to provide a theoretical basis for the clinical treatment of patients. METHODS: Relevant literatures from the establishment of the database to December 31, 2020, were searched from databases such as PubMed. The literatures with randomized controlled trial of the clinical efficacy of glucocorticoids in the treatment of RA and SLE were screened for meta-analysis. RESULTS: Eleven documents were included, including 1,298 participants. It was found that the cardiovascular system [mean difference (MD) =1.23; 95% confidence interval (CI): 0.64 to 2.34; Z=0.62; P=0.53], respiratory system (MD =1.87; 95% CI: -0.66 to 5.29; Z=1.18; P=0.24), nervous system (MD =1.22; 95% CI: 0.25-5.84; Z=0.25; P=0.8), visual impairment (MD =1.41; 95% CI: 0.79-2.52; Z=1.15; P=0.25), endocrine system (MD =8.53; 95% CI: 2.71-26.88; Z=3.66; P=0.0003), digestive system (MD =1.41; 95% CI: 0.76-2.63; Z=1.09; P=0.28), genitourinary system (MD =1.06; 95% CI: 0.35-3.17; Z=0.1; P=0.92), blood system (MD =2.96; 95% CI: 0.62-14.26; Z=1.35; P=0.18), Z=0.48; P=0.63), infection status (MD =1.36; 95% CI: 0.98-1.87; Z=1.86; P=0.06), clinical efficacy (MD =1.79; 95% CI: 1.27-2.52; Z=3.32; P=0.0009), pain (MD =1.16; 95% CI: 0.76-1.78; Z=0.68; P=0.5), and joint swelling score (MD =0.03; 95% CI: -0.38 to 0.45; Z=0.15; P=0.88) of experimental group after treatment were all superior versus controls. However, the skin and mucous membranes (MD =0.87; 95% CI: 0.55-1.37; Z=0.61; P=0.54), musculoskeletal (MD =0.85; 95% CI: 0.43-1.66; Z=0.48; P=0.63), radiation injury (MD =-1.93; 95% CI: -3.68 to -0.18; Z=2.17; P=0.03), and C-reactive protein (CRP) level (MD =-8.66; 95% CI: -10.16 to -7.16; Z=11.34; P<0.00001) of experimental group were inferior to those of control group. DISCUSSION: Glucocorticoids in the treatment of RA and SLE can improve the clinical efficacy, but it was easy to cause multiple system adverse reactions. Therefore, the clinical treatment should follow the doctor's advice.

Amelioration of Juglanin against LPS-Induced Activation of NLRP3 Inflammasome in Chondrocytes Mediated by SIRT1.

Arthritis is characterized by irreversible joint destruction and presents a global health burden. Natural alternatives to synthetic drugs have been gaining popularity for their safety and effectiveness. Juglanin has demonstrated a range of anti-inflammatory effects in various tissues and cell types. However, the pharmacological function of Juglanin in arthritis and chondrocytes has been little studied. ATDC5 cells were treated with 1 µg/mL lipopolysaccharide (LPS) in the presence or absence of juglanin (2.5, 5 µM) for 24 h. The effects of juglanin on cellular nucleotide-binding domain leucin-rich repeat receptor 3 (NLRP3) inflammasome complex and endproduct interleukin 1ß (IL-1ß) and interleukin (IL-18) were assessed by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot experiments. The oxidative stress was measured by super oxide dismutase (SOD) activity and NADPH oxidase 4 (NOX4) expression. The dependent effect of juglanin on silent information regulator 2 homolog 1 (SIRT1) was evaluated by siRNA knockdown approach. Juglanin significantly reduced cellular oxidative stress by downregulating NOX4 expression production and rescuing the decreased activity of total SOD induced by LPS. Juglanin inhibited the activation of the TxNIP/NLRP3/ASC/caspase-1 axis, and decreased production of IL-1ß and IL-18. Moreover, juglanin rescued the LPS-induced decrease in SIRT1 expression. SIRT1 silencing abolished the anti-NLRP3 inflammasome effect of juglanin, indicating that the effects of juglanin are dependent on its amelioration on SIRT1 expression. Juglanin possesses an anti-inflammatory and anti-ROS capacity in chondrocytes, and this study provides available evidence that juglanin may be of use in the treatment of arthritis.

KLF15 Regulates the Expression of MMP-3 in Human Chondrocytes.

Imbalance of metabolism on catabolic and anabolic molecules in chondrocytes has been associated with the cartilage damage in osteoarthritis (OA). Matrix metalloproteinase-3 (MMP-3), one of the most important catabolic factors, acts as a cartilage-degrading enzyme, which is associated with the degradation of type II collagen and aggrecan. Kruppel-like factor 15 (KLF15), an important member of the KLFs family, possesses a variety of biological functions. However, the physiological roles of KLF15 in chondrocytes and the pathological progression of OA remain unknown. In the current study, we report that KLF15 is expressed in primary chondrocytes as well as ATDC5 and SW1353 chondrogenic cell lines. Interestingly, KLF15 expression was significantly lower in chondrocytes from OA patients compared with those from normal subjects. Also, we found that tumor necrosis factor α (TNF-α) treatment reduced the expression of KLF15 mediated by p53 in human chondrocytes. Notably, it was shown that KLF15 reduced TNF-α-induced expression of MMP-3 at the transcriptional level. Mechanistically, the chromatin immunoprecipitation assay displayed that KLF15 could bind to the promoter region of MMP-3. Our results suggest that KLF15 might be a novel therapeutic target of OA.

Anti-apoptotic effect of interleukin-22 on fibroblast-like synoviocytes in patients with rheumatoid arthritis is mediated via the signal transducer and activator of transcription 3 signaling pathway.

AIM: Inadequate apoptosis of fibroblast-like synoviocytes (FLS) plays a crucial role in the immunopathogenesis of rheumatoid arthritis (RA). Interleukin-22 (IL-22) is a novel member of the cytokine network that has been found to be involved in the immunological process underlying RA. In this study, we investigated the effect of IL-22 on the survival of RA-FLS from RA patients and examined the possible mechanism to determine new therapeutic strategies for RA. METHODS: FLS obtained from patients with RA were cultured in vitro and treated with sodium nitroprussiate (SNP) to induce apoptosis in the presence or absence of IL-22. RA-FLS viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RA-FLS apoptosis was analyzed by annexin V/propidium iodide staining (AV/PI). The levels of IL-22R1, pSTAT3-Y705, pSTAT3-S727, total STAT3, Bcl-xL and Bcl-2 were detected by Western blot analysis. RESULTS: IL-22R1 was expressed on RA-FLS. IL-22 pretreatment at concentrations ranging from 10 to 100 ng/mL increased RA-FLS viability and prevented SNP-induced apoptosis. Treatment with the STAT3 inhibitors, HO3867 or STA21, reversed the protective effect of IL-22 on SNP-induced apoptosis of RA-FLS. IL-22-induced phosphorylation of STAT3 (pSTAT3-Y705 and pSTAT3-S727) was increased in RA-FLS. Also IL-22 increased Bcl-2 expression in SNP-treated RA-FLS, and the effect was reversed by treatment with HO3867 or STA21. CONCLUSION: IL-22 protects against SNP-induced apoptosis in RA-FLS by activating the STAT3 pathway and the downstream target gene, Bcl-2. Therefore, therapeutic strategies that target the IL-22/STAT3 pathway are implicated as candidates for RA treatment.