Inflammatory markers and risk factors of RA patients with depression and application of different scales in judging depression.

To evaluate the association of inflammatory markers and depression in RA patients and the risk factors in RA with depression, a cross-sectional study was conducted in a cohort of RA patients from southern China.Two hundred-fifteen RA patients were enrolled. The demographic and disease-related characteristics were recorded and inflammatory markers in sera were measured. RA patients were guided to fill out PHQ-9 scale by themselves, the psychological state was evaluated by psychiatry experts and graded according to the HAMD-17 scale. The consistency of the two scales in judging depression was evaluated. RA with depression group had HAMD-17 scores greater than 7. The levels of CRP, ESR, fibrinogen, SAA, IL-2, IL-6, TNF-α, IFN-γ, IL-4, and IL-10 were measured and compared. Logistic regression analysis was performed to find the risk factors of RA with different depression levels. One hundred-five (48.84%) RA patients had HAMD-17 scores greater than 7. High consistency was found between HAMD-17 and PHQ-9 in predicting depression. RA patients with depression were more likely to have tender joints, lower income, no employment, higher disease activity, joint deformities and glucocorticoid treatment. The depressed RA patients had higher serum levels of IL-6, CRP, fibrinogen, and SAA. IL-6, CRP, fibrinogen, and SAA were positive correlated with depression in RA patients. PHQ-9 can replace HAMD-17 in clinical application to judge depression.

miR-98 Modulates Cytokine Production from Human PBMCs in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.

OBJECTIVE: There is evidence that interleukin-6 (IL-6) upregulation plays a critical role in immunopathology of systemic lupus erythematosus (SLE). MicroRNA- (miRNA-) 98 was predicted to bind with the 3'-untranslated region (3'-UTR) of IL-6 gene. We hypothesized miR-98 through its regulation of IL-6 gene expression to influence cytokine production from peripheral blood mononuclear cells (PBMCs) in SLE. METHODS: The expression of miR-98 and IL-6 mRNA in the PBMCs of 41 SLE patients and 20 healthy controls (HC) was detected by quantitative reverse transcription PCR (qRT-PCR). The correlations between miR-98 expression and clinical features were evaluated. Luciferase reporter assay was performed to identify miR-98 targets. miR-98 mimics, miR-98 inhibitor, and IL-6 overexpression vector were generated. Cell viability of PBMCs was assessed using MTT assay. Gene expression and protein level were determined by qRT-PCR and Western blotting. TNF-α, IL-8, IL-1ß, and IL-10 levels in cultured supernatants were quantified using ELISA. RESULTS: The expression of miR-98 was downregulated in PBMCs of SLE patients, and its expression is negatively associated with IL-6 levels. miR-98 expression was correlated with disease activity, lupus nephritis, and anti-dsDNA antibody. IL-6 mRNA was a target gene of miR-98. IL-6 overexpression promoted the proliferation of PBMCs and increased the levels of TNF-α, IL-8, IL-1ß, and IL-10. Those effects were further enhanced by miR-98 inhibitor, while were suppressed by miR-98 mimics. miR-98 regulated the levels of STAT3 phosphorylation via its target gene IL-6. CONCLUSION: The current study revealed that miR-98 could ameliorate STAT3-mediated cell proliferation and inflammatory cytokine production via its target gene IL-6 in patients with SLE. These results suggest that miR-98 might serve as a potential target for SLE treatment and other IL-6-mediated diseases.

Prolactin increases tumor necrosis factor alpha expression in peripheral CD14 monocytes of patients with rheumatoid arthritis.

Tumor necrosis factor (TNF)-α is one of the major proinflammatory mediators of rheumatic arthritis (RA); the regulatory factors for TNF-α release is not fully understood. This study aims to investigate the role of prolactin receptor (PRLR) activation in regulating the expression and release of TNF-α from CD14(+) monocytes. The results showed that the expression of PRLR was detectable in CD14(+) monocytes of healthy subjects, which was markedly increased in RA patients. Exposure to PRL in the culture increased the expression and release of TNF-α from CD14(+) monocytes, which was abolished by the PRLR gene silencing or blocking the mitogen activated protein (MAPK) pathway. We conclude that exposure to PRL increases TNF-α release from CD14(+) monocytes of RA patients, which can be abolished by PRLR gene silencing or treating with MAPK inhibitor.