Guo-Cui Wu

Increased serum interleukin 17 in patients with systemic lupus erythematosus

Interleukin 17 (IL-17) is a Th17 cytokine associated with inflammation, autoimmunity and defense against some bacteria, it has been implicated in many chronic autoimmune diseases including psoriasis, multiple sclerosis and systemic sclerosis. However, whether IL-17 plays a role in the pathogenesis of systemic lupus erythematosus (SLE) remains unclear. In the present study, we aimed to investigate the serum IL-17 level in patients with SLE and it’s associations with disease manifestations and activity. Fifty-seven patients with SLE and 30 healthy volunteers were recruited. Serum IL-17 levels were examined by enzyme linked immunosorbent assay (ELISA). Statistic analyzes were performed by SPSS 10.01. Results show that serum IL-17 levels were significantly elevated in SLE patients as compared with normal controls. Nevertheless, no associations of serum IL-17 level with clinical and laboratory parameters were found; no significant difference regarding serum IL-17 level between SLE patients with nephritis and those without nephritis was found; no significant difference was found between Less active SLE and More active SLE; Correlation analysis between serum IL-17 levels and SLEDAI showed no association. Taken together, our results indicate increased serum IL-17 levels in SLE patients, suggesting that this cytokine may trigger the inflammatory process in SLE. However, no associations of serum IL-17 level with disease manifestations were found. Therefore, further studies are required to confirm this preliminary data.

Emerging role of long noncoding RNAs in autoimmune diseases.

Long noncoding RNA (lncRNA), with size larger than 200 nucleotides, is a new class of noncoding RNA. Emerging evidence has revealed that lncRNAs play a key role in the regulation of immunological functions and autoimmunity. Herein, we review the recent findings of lncRNA regulation in immune functions and in the development of autoimmunity and autoimmune disease. In addition, we focus on the involvement of lncRNA regulation in innate and adaptive immune responses, immune cell development, and differential expression of lncRNAs in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), multiple sclerosis (MS), autoimmune thyroid disease (AITD), psoriasis, polymyositis/dermatomyositis (PM/DM) and Crohns disease (CD).

Decreased serum IL-22 levels in patients with systemic lupus erythematosus

Normal controls 30 340.19 (212.45–586.62) SLE 57 36.00 (26.69–54.85) b0.001 SLE without nephritis 30 39.75 (28.33–56.55) SLE with nephritis 27 31.41 (21.50–51.47) NS Less active SLE 16 36.85 (26.33–52.38) More active SLE 41 36.00 (26.69–55.82) NS a vs normal controls. b vs SLE without nephritis. c vs less active SLE. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, characterized by a multitude of autoantibody production, complement activation and immune-complex deposition, which causes tissue and organ damage. The etiology and pathogenetic mechanisms of SLE have not been clearly elucidated. Cytokines produced by abnormal T-helper (Th) cells have been shown to be involved in the pathogenesis of SLE [1]. Activated T cells have been indicated to differentiate into memory/effector T cells that are classified into T helper 1 (Th1) and Th2 subsets based on their cytokine production profiles [2]. Until recently, Th1 dominant immune responses have been generally considered to be pathological in autoimmune disease via the induction of inflammatory reaction, and large amounts of Th1 cytokines such as interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and IL-12 have been found in SLE [3,4]. However, there are growing evidences that a recently recognized subset of Tcells, named Th17 cells have been implicated in the etiology of autoimmune disease including SLE and systemic scleroderma [1,5]. Th17 cells are a novel subset of Th cells that selectively secrete several proinflammatory cytokines, including IL-17, IL23 and IL-22 [6]. It has been shown that IL-17 is involved in tissue pathology in autoimmune models, and anti-IL-17 reduced joint inflammation and bone erosion in an experimental arthritis model. In addition, previous studies have shown that the increased production of IL-17 exerts a synergistic effect on the inflammatory reactions to induce increased production of a panel of proinflammatory cytokines including IFN-[gamma], IL-2 and granulocyte monocyte-colony stimulating factor in SLE [7]. Dong et al. found that IL-17might play an important role in the pathogenesis of lupus nephritis through the induction of IgG, anti-dsDNA overproduction and IL-6 overexpression of PBMC in patients with lupus nephritis [8]. A recent study also indicated hyperproduction of IL-23 and IL-17 in patients with SLE [9]. Nevertheless, whether IL-22 plays a role in the pathogenesis of SLE is still unclear and remains to be established. The assessment of a cytokine at the serum level would certainly simplify clinical evaluation [10]. Therefore, in the present study, we investigated serum IL-22 levels in SLE, in comparison with normal controls, and relations to disease activity. Fifty-sevenpatientswith SLE (55 females, 2males;mean age 36±13 y, range 16–60 y) were recruited from the Departments of Rheumatology at Anhui Provincial Hospital. The diagnosis of SLE was established by the presence of four or more American College of Rheumatology (ACR) diagnostic criteria [11]. Renal involvementof SLEwasdefinedaccording to the ACR criteria, i.e., any one of the following: 1) persistent proteinuria ≥0.5g/day; 2) thepresenceof active cellular casts; or 3) biopsyevidenceof lupus nephritis [12]. Individual disease activity was quantified using the SLEdisease activity index (SLEDAI) score [13].More active SLEwasdefined as a SLEDAI score ≥10, those patientswith SLEDAIb10were classed as less active. 30 healthy volunteers (29 females, 1 male; mean age 44±12 y, range from 15 to 66 y) were included as normal controls, all of them did

Glucocorticoids increase impairments in learning and memory due to elevated amyloid precursor protein expression and neuronal apoptosis in 12-month old mice.

Alzheimers disease is a chronic neurodegenerative disorder marked by a progressive loss of memory and cognitive function. Stress level glucocorticoids are correlated with dementia progression in patients with Alzheimers disease. In this study, twelve month old male mice were chronically treated for 21 days with stress-level dexamethasone (5mg/kg). We investigated the pathological consequences of dexamethasone administration on learning and memory impairments, amyloid precursor protein processing and neuronal cell apoptosis in 12-month old male mice. Our results indicate that dexamethasone can induce learning and memory impairments, neuronal cell apoptosis, and mRNA levels of the amyloid precursor protein, beta-secretase and caspase-3 are selectively increased after dexamethasone administration. Immunohistochemistry demonstrated that amyloid precursor protein, caspase-3 and cytochrome c in the cortex and CA1, CA3 regions of the hippocampus are significantly increased in 12-month old male mice. Furthermore, dexamethasone treatment induced cortex and hippocampus neuron apoptosis as well as increasing the activity of caspase-9 and caspase-3. These findings suggest that high levels of glucocorticoids, found in Alzheimers disease, are not merely a consequence of the disease process but rather play a central role in the development and progression of Alzheimers disease. Stress management or pharmacological reduction of glucocorticoids warrant additional consideration of the regimen used in Alzheimers disease therapies.

Subclinical atherosclerosis in patients with systemic lupus erythematosus: A systemic review and meta-analysis

OBJECTIVE Systemic lupus erythematosus (SLE) is associated with increased risk of cardiovascular disease. Carotid intima media thickness (CIMT) and carotid plaques are both frequently used to identify populations at higher cardiovascular risk. A systematic literature search and meta-analysis were performed to evaluate CIMT and carotid plaques difference between SLE patients and normal controls. METHODS The literatures comparing markers of cardiovascular risk (CIMT and prevalence of carotid plaques) in SLE and controls were systematically searched in PubMed, EMBASE and Cochrane databases. The overall mean CIMT difference and pooled odds ratio (OR) for the prevalence of carotid plaques between SLE patients and control groups were calculated by fixed-effects or random-effect model analysis. Meta-regression was performed to explore the potential influencing factors. Publication bias was examined by a funnel plot and Eggers test. RESULTS A total of 80 studies (6085 SLE patients and 4794 controls) were included in the final analysis, 71 studies with data on CIMT (4814 cases and 3773 controls) and 44 studies reporting on the prevalence of carotid plaques (4417 cases and 3528 controls). As compared to controls, SLE patients showed a higher CIMT (WMD: 0.07 mm; 95%CI: 0.06, 0.09; P<0.001), and an increased prevalence of carotid plaques (OR: 2.45; 95%CI: 2.02, 2.97; P<0.001). Meta-regression models showed that traditional cardiovascular risk factors (age, HDL and triglyceride of SLE patients) and lupus related risk factors (as expressed by duration, ESR, SLEDAI and steroids) had a significant influence on CIMT, steroids and triglyceride had significant influence on the prevalence of carotid plaques. CONCLUSIONS Our findings support the current evidence base for an increased cardiovascular burden in SLE patients and support the use of CIMT and carotid plaques in observational studies in SLE patients. The findings are of importance to design more specific prevention and treatment strategies.

Anti-neutrophil Cytoplasmic Antibodies in New-onset Systemic Lupus Erythematosus and Lupus Nephritis

This study aims to investigate the role of Antineutrophil cytoplasmic antibodies (ANCA) in patients with new-onset systemic lupus erythematosus (SLE). Sixty SLE patients, 28 of whom had lupus nephritis (LN), and 60 normal controls were enrolled; Serum ANCA was measured by enzyme linked immunosorbent assay (ELISA). The clinical and laboratory parameters of the patients were also recorded. Results show that twenty SLE patients were seropositive for ANCA, which was significantly higher than in normal controls. LN patients had significantly higher positive rate of ANCA than patients without nephritis. Compared with ANCA-negative patients, the ANCA-positive patients had significantly higher incidence of nerves system disorder, myocarditis, renal involvement and serositis. The positive rate of γ-globulin, anti-dsDNA and anti-Sm antibodies were significantly higher in ANCA-positive patients. Elevated IgG and ESR, decreased serum C3/C4 appeared more often in ANCA-positive patients. In addition, serum ANCA level correlated positively with disease activity. Taken together, ANCA might be used as a potential complementary parameter to differentiate LN from SLE without nephritis. In addition, ANCA may serve as a useful marker of the disease activity of SLE.

Protective Effect of Astragaloside on Focal Cerebral Ischemia/Reperfusion Injury in Rats

This study was to observe the neurological protective effects of astragalosides (AST) on focal cerebral ischemia-reperfusion (I/R) injury in rats and to explore its possible mechanism. Male SD rats received right middle cerebral artery occlusion for 120 min and AST (40 mg/kg) was orally administered. The rats were decapitated 1, 3, 7, and 14 days after reperfusion. The neurological deficit score, infarct volume and water content of brain were measured; the activity of superoxide dismutase (SOD), lactate dehydrogenase (LDH) and nitric oxide synthase (NOS), and the content of malondialdehyde (MDA), lactate (LD) and nitric oxide (NO) of brain tissue were detected too. The expression of inducible nitric synthase (iNOS), nerve growth factor (NGF) and tropomyosin receptor kinase A (TrkA) mRNA were measured by RT-PCR or real-time PCR. AST could significantly reduce the neurological deficit score; infract volume and water content, increase SOD and LDH activities, decrease NOS activity and MDA, LD and NO content. AST treatment could down-regulate expression of iNOS mRNA, while, NGF and TrkA mRNA were up-regulated. Our data suggest that AST have the protective effects on focal cerebral ischemia in rats at the different reperfusion time points, the mechanism may be related to the antioxidation, regulated the expressions of iNOS, NGF and TrkA mRNA.

High Mobility Group Box 1: a potential therapeutic target for systemic lupus erythematosus

High Mobility Group Box 1 (HMGB1) is a nuclear protein participating in chromatin architecture and transcriptional regulation. Recently, there is increasing evidence that HMGB1 contributes to the pathogenesis of chronic inflammatory and autoimmune diseases due to its pro-inflammatory and immunostimulatory properties. Elevated expression of HMGB1 was found in the sera of patients and mice with systemic lupus erythematosus (SLE). In addition, it has been shown that HMGB1 may act as a proinflammatory mediator in antibody-induced kidney damage in SLE. All theses findings suggest that HMGB1 have important biological effects in autoimmunity that might be a promising therapeutic target for SLE. In this review, we will briefly discuss the biological features of HMGB1 and summarize recent advances on the role of HMGB1 in the pathogenesis and treatment of SLE.

Subclinical Atherosclerosis in Patients With Inflammatory Bowel Diseases A Systematic Review and Meta-Analysis

We evaluated the differences in major markers of cardiovascular (CV) risk between inflammatory bowel diseases (IBDs) and controls by a systematic review and a meta-analysis. We searched PubMed, EMBASE, and Cochrane databases for literature comparing CV risk markers in IBDs and controls. The overall mean carotid intima-media thickness (CIMT), flow-mediated dilation (FMD%), and carotid-femoral pulse wave velocity (cfPWV) difference between patients with IBDs and control groups were calculated. Twenty-eight studies were included in the meta-analysis, including 16 studies with data on CIMT, 7 studies reporting FMD%, and 9 studies on cfPWV. Compared to controls, patients with IBDs showed significantly higher CIMT (standardized mean difference [ SMD]: 0.534 mm; 95% confidence interval [CI], 0.230 to 0.838; P = .001), significantly lower FMD% ( SMD, -0.721%; 95% CI, -1.020 to -0.421; P < .0001), and significantly increased cfPWV ( SMD, 0.849; 95% CI, 0.589 to 1.110; P < .0001). When analyzing subgroups with ulcerative colitis and Crohn disease (CD), all results were still significant except CIMT in CD. Our findings support the current evidence for an elevated CV burden in patients with IBD and support the clinical utility of markers of subclinical atherosclerosis in the management of these patients.

Identification of long non-coding RNAs GAS5, linc0597 and lnc-DC in plasma as novel biomarkers for systemic lupus erythematosus.

Despite increasing evidence that long non-coding RNAs (lncRNAs) widely take part in human diseases, the role of lncRNAs in systemic lupus erythematosus (SLE) is largely unknown. In this study, we performed a two-stage study to explore the plasma levels of five lncRNAs (GAS5, linc0949, linc0597, HOTAIRM1 and lnc-DC) and their potential as SLE biomarkers. Compared with healthy controls, plasma levels of GAS5 and lnc-DC were significantly decreased (P < 0.001 and P = 0.002, respectively) while linc0597 were overexpressed in SLE patients (P < 0.001). When SLE patients were divided into SLE without nephritis and lupus nephritis (LN), the levels of lnc-DC were significantly higher in LN compared with SLE without nephritis (P = 0.018), but no significant difference in levels of GAS5 and linc0597 were found between LN and SLE without nephritis; plasma linc0949 level showed no significant difference in all comparisons. Further evaluation on potential biomarkers showed that GAS5, linc0597 and lnc-DC may specifically identify patients with SLE, the combination of GAS5 and linc0597 provided better diagnostic accuracy; lnc-DC may discriminate LN from SLE without nephritis. In summary, GAS5, linc0597 and lnc-DC in plasma could be potential biomarkers for SLE.