The Antimicrobial Peptide Esculentin-1a(1-21)NH2 Stimulates Wound Healing by Promoting Angiogenesis through the PI3K/AKT Pathway.

Delayed wound healing is a persistent medical problem mainly caused by decreased angiogenesis. Esculentin-1a(1-21)NH2 [Esc-1a(1-21)NH2], has broad-spectrum antibacterial properties which comes from frog skins. It has shown promise as a treatment for wound healing. However, its effects on angiogenesis as well as the mechanism by which esc-1a(1-21)NH2 enhanced wound healing remained unclear. In this study, we analyzed the structural properties and biocompatibility of esc-1a(1-21)NH2 and evaluated its effect on wound closure using a full-thickness excision model in mice. Our results showed that esc-1a(1-21)NH2 significantly accelerated wound healing by increasing collagen deposition and angiogenesis, characterized by elevated expression levels of platelet, endothelial cell adhesion molecule-1 (CD31) and proliferating cell nuclear antigen (PCNA). Furthermore, the angiogenic activity of esc-1a(1-21)NH2 was confirmed in vitro by various assays. Esc-1a(1-21)NH2 significantly promoted cell migration and cell proliferation in human umbilical vein vascular endothelial cells (HUVECs) via activation of the phosphatidylinositol 3'-kinase (PI3K)/protein kinase B (AKT) pathway, and upregulated the expression of CD31 at both mRNA and protein levels. The effect of esc-1a(1-21)NH2 on angiogenesis was diminished by LY294002, a PI3K pathway inhibitor. Taken together, this study demonstrates that esc-1a(1-21)NH2 accelerates wound closure in mice by promoting angiogenesis via the PI3K/AKT signaling pathway, suggesting its effective application in the treatment of wound healing.

Anti-fibrotic effect of iguratimod on pulmonary fibrosis by inhibiting the fibroblast-to-myofibroblast transition.

PURPOSE: Pulmonary fibrosis (PF) is a severe lung disease causing significant morbidity and mortality. PF pathogenesis is attributed to the fibroblast-to-myofibroblast transition (FMT) driven by the most potent pro-fibrogenic factor TGF-ß1 activating the Smad3-dependent TGF-ß1 canonical pathway. Iguratimod (IGU) is a novel anti-rheumatic drug that suppresses the secretion of inflammatory factors, but is also able to modulate the differentiation of multiple cells. Therefore, the aim of this work was to investigate the effect of IGU on FMT. MATERIALS/METHODS: PF mouse model was induced in C57BL/6 male mice by bleomycin. The effect of IGU was assessed through the evaluation of lung morphology by H&E and through the collagen accumulation in the lung by Masson staining. Primary human lung fibroblasts (pHLFs) were also used to evaluate the effect of IGU in vitro on TGF-ß1-stimulated cells, and proliferation, migration and invasion were measured, together with genes and proteins involved in FMT. RESULTS: IGU attenuated bleomycin-induced PF in mice and improved the pathological changes in their lungs. In addition, IGU significantly inhibited proliferation, migration and invasion in TGF-ß1-stimulated pHLFs without causing apoptosis. Moreover, IGU significantly reduced TGF-ß1-induced increase of collagen I and III mRNA expression, thus reducing lung function impairment, and α-SMA, Smad2 and Smad3 phosphorylation, fibronectin expression and F-actin microfilament formation, thus attenuating FMT through the inhibition of the Smad3 pathway. CONCLUSIONS: Our results collectively revealed the beneficial effect of IGU on the inhibition of FMT, thus suggesting that it might act as an effective anti-fibrotic agent in preventing the progression of PF.

Clinical Characteristics and Risk Factors of Diffuse Alveolar Hemorrhage in Systemic Lupus Erythematosus: a Systematic Review and Meta-Analysis Based on Observational Studies.

Diffuse alveolar hemorrhage (DAH) is a rare but potentially deadly manifestation of systemic lupus erythematosus (SLE). The aim of this study was to investigate the clinical characteristics and risk factors of DAH in SLE. A systematic review and meta-analysis of previous observational studies compared the clinical characteristics and risk factors between DAH-SLE and SLE patients without DAH. A total of 5 observational studies were included in this meta-analysis. Compared with the SLE patients without DAH, DAH-SLE patients had a significantly higher incidence of neuropsychiatric events (OR = 4.321, 95% CI (1.686-11.073), P = 0.002, I2 = 49.2%), nephritis (OR = 3.146, 95% CI (1.663-5.955,), P = 0.000, I2 = 0.0%), serositis (OR = 6.028, 95% CI (1.418-25.635), P = 0.015, I2 = 80.3%), dyspnea (OR = 31.241,95% CI (0.202-4833.203), P = 0.181, I2 = 94.6%), and a significantly lower level of C3 (SMD = - 1.358, 95% CI - 1.685, - 1.031), P = 0.000, I2 = 98.0%), C4 (SMD = - 1.251, 95% CI (- 1.648, - 0.855), P = 0.000, I2 = 87.7%), hemoglobin (SMD = - 2.074, 95% CI (- 2.433, - 1.715), P = 0.000, I2 = 94.2%), and a higher SLEDAI-2K score (SMD = 1.284, 95% CI (0.959, 1.608), P = 0.000, I2 = 98.2%). However, due to significant heterogeneity, some of these results should be interpreted cautiously. Nevertheless, when the above abnormal indicators are found, especially neuropsychiatric involvement and nephritis, besides the existed diagnostic criteria for DAH in SLE patients, a diagnosis for DAH should be considered and relevant treatment timely initiated. Further prospective multi-center SLE studies with a large cohort of patients and long-term follow-up are needed to clarify further or find out the specific clinical indexes for DAH in SLE patients.

The incidence of extra-articular manifestations in southern Chinese patients with inflammatory joint diseases.

AIM: Inflammatory joint diseases (IJDs) are chronic arthritis, but frequently present with co-morbidities of other organs and systems, which is known as extra-articular manifestations (EAMs). It is still unclear which clinical characteristics or bio-markers can predict the development of EAMs. The aim of this study was to estimate the proportion of EAMs in southern Chinese patients with IJDs and to explore the risk factors. METHODS: This was a retrospective cohort study of a total 1135 IJDs patients, including 788 rheumatoid arthritis (RA) patients, 307 ankylosing spondylitis (AS) patients and 40 psoriatic arthritis (PsA) patients. Demographic data, disease characteristics, laboratory blood tests, medical imaging, and the presence of EAMs were recorded. RESULTS: We found 459 (40.44%) patients presented with EAMs: 30.84% had cardiovascular involvement, 7.67% had pulmonary involvement, 5.29% had osteoporosis/low bone mineral density, 2.29% had ocular, 0.79% had gastrointestinal and 0.26% had renal involvements. Multivariate logistic regression showed older age (odds ratio [OR] 1.06, P < .001) and higher anti-cyclic citrullinated peptide antibody (anti-CCP) levels (OR 1.003, P = .019) were independent risks of EAMs in RA patients. In the AS group, older age (OR 1.07, P < .001) and higher disease activity (OR 3.24-7.42, both P < .05), were independent risks of EAMs. In the PsA group, longer disease duration (OR 1.01, P = .036) and higher disease activity (OR 1.15, P = .004) were univariate associated factors. CONCLUSION: These results suggested the high prevalence of EAMs, and it is important to regularly screen for EAMs, as they influence treatment decisions and impact on patients' quality of life.

Thrombocytopenia as a Prognostic Marker for Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) patients often exhibit hematological abnormalities, but the role of thrombocytopenia on the prognosis of SLE shows inconsistent results. The purpose of this meta-analysis was to confirm the impact of thrombocytopenia on mortality and end organ damage in patients with SLE. MATERIALS AND METHODS: Three electronic databases, PubMed, Embase and Cochrane library were systematically searched to identify the eligible studies from inception to November 2017 in order to evaluate the impact of thrombocytopenia on the prognosis of patients with SLE. The summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to measure the impact of thrombocytopenia on mortality and end organ damage based on the random-effects model. RESULTS: A total of 8 studies that reported data on 2,158 patients with SLE were included. The summary OR indicated that SLE subjects with thrombocytopenia were significantly associated with an increased risk of mortality (OR: 4.57; 95% CI: 2.28-9.17; P < 0.001) and end-organ damage (OR: 3.31; 95% CI: 1.11-9.86; P = 0.031). Furthermore, the sensitivity analysis indicated stable mortality, while the result for end organ damage was variable. In addition, the patients with thrombocytopenia with disease duration <60 months presented a greater risk for mortality than those with disease duration ≥60.0 months (P = 0.002). CONCLUSIONS: Patients with SLE and thrombocytopenia were found to be associated with an increased risk of mortality and end organ damage.

Acquired hypophosphatemic osteomalacia is easily misdiagnosed or neglected by rheumatologists: A report of 9 cases.

The aim of the present study was to assist rheumatologists in differentiating hypophosphatemic osteomalacia (HO) from mimic rheumatology diseases. Clinical data was obtained from 9 patients with acquired HO, initially misdiagnosed as mimic rheumatologic diseases. The data were retrospectively analyzed and a literature review was performed. The etiology of the cases was as follows: Adefovir dipivoxil-induced Fanconi syndrome was present in 6 of the cases, 2 were tumors and 1 case was chronic nephropathy. The chief complaint was thoracic or back pain and arthralgia, followed by progressive muscle weakness and dramatic movement limitation. All patients were transferred to 3-6 hospitals for extended periods due to misdiagnosis with conditions such as ankylosing spondylitis, chronic arthritis, lumbar disc disease, osteoporosis and somatoform disorder. Hypophosphatemia was observed in the patients and bone scans revealed diffusely decreased tracer uptake, with multiple hot spots of fractured sites and involved joints. Furthermore, patients' bone density was markedly low compared with the normal range for their age and sex. In the present study, 6 of the patients recovered when adefovir dipivoxil was stopped. In 1 case, hypophosphatemia was ameliorated following tumor resection. The remaining patients, 1 with sub-skull tumor and 1 with chronic kidney disease, had poor prognoses due to incurable diseases. In conclusion, diagnosing HO is challenging for rheumatologists and physicians. Basic examinations of electrolyte balance and bone mineral density should be performed, as should tumor screening and a careful collection of patient medical history and drugs in young patients with unexplained thoracic or back pain and muscle weakness. Removing any secondary etiology, such as drugs may dramatically improve the patients clinical manifestations and result in an improved prognosis.

[Adefovir dipivoxil-induced Fanconi syndrome and hypophosphatemic osteomalacia associated with muscular weakness in a patient with chronic hepatitis B].

Adefovir dipivoxil is commonly used for treatment of chronic hepatitis B. The renal toxicity of adefovir dipivoxil is dose- and time-related, occurring often in patients with a daily dose over 30 mg and those with impaired renal function. We report a case of chronic hepatitis B with a history of taking adefovir dipivoxil at 10 mg/day for 4 years. The patient complained of lumbosacral and joint pain and had the diagnosis of ankylosing spondylitis (AS) or spondyloarthropathy in several hospitals before admission in our hospital. A diagnosis of acquired Fanconi syndrome and hypophosphatemia osteomalacia associated with progressive muscular weakness was made eventually. We reviewed the literature and found reports of only fewer than 10 similar cases. Clinical attention should be given to kidney damage induced by adefovir dipivoxil.

[Neonatal lupus erythematosus: a report of 7 cases and review of 87 cases of China].

OBJECTIVE: To acquire more knowledge about neonatal lupus erythematosus (NLE). METHOD: Seven cases with neonatal lupus erythematosus who were seen in this hospital from 1990 to 2009 are reported in this paper and 87 cases reported previously from 1980 to now in China were reviewed. The clinical manifestations, serum autoantibodies, treatment and results of long-term follow-up are analyzed and summarized. RESULT: Totally 94 cases were summarized. Male/female ratio was 48/46; 73 cases had skin rash; 23 had heart abnormality, among whom 13 had cardiac conductive problems including 8 cases of atrioventricular blockage (AVB) (3 degree I, 3 degree II and 2 degree III) and 5 cases of right bundle branch block cases (RBBB). Nine cases had anatomical abnormality including 5 cases of atrial septal defect (ASD), 2 cases of ventricular septal defect (VSD) and 2 cases of atrial enlargements. Forty-four cases had hematological problems including 28 with thrombocytopenia, 11 with leukocytopenia and 34 with anemia. Thirty cases had hepatic abnormality, including 24 liver dysfunction, 22 hepatomegaly, 6 splenomegaly and 3 cholestasis. Three cases had nephropathy; 3 had elevated creatine kinase; 2 had nervous disorder. Among the 94 cases, 86 (91.5%) were positive for anti-SSA, 51 (54.3%) anti-SSB, 16 anti-ds-DNA, 14 anti-U1-RNP, 13 anti-Sm (+), 6 anti-RNP and 4 anti-rRNP(+). Among the corresponding mothers, 39 cases (44.8%) were asymptomatic before pregnancy, 35 had SLE, 5 had SCLE, 3 had Sjogren syndrome, 2 had chilblain, photosensitivity and arthralgia, respectively, 1 had rheumatoid arthritis and 1 had psoriasis. During pregnancy, 8 mothers developed SLE. Totally 48 mothers (51.1%) suffered from LE. Together with 15 mothers who had transient skin rash during the pregnancy, there were 23 mothers (59%) who had new clinical manifestation among the 39 asymptomatic mothers. Twenty NLE cases accepted glucocorticoid treatment, 4 of them were treated with intravenous immunoglobulin. Sixty-eight cases were followed up for up to 12 years, 58 cases were healthy, 5 cases improved and 3 died. Two cases still had grade III AVB without pacemaker. CONCLUSION: NLE is a rare acquired autoimmune disease. Although nearly half of the mothers were asymptomatic before pregnancy, more than half of them developed LE or other symptoms. The clinical presentations in Chinese cases include a transient rash, cardiac lesion while grade III AVB was rare, hematological changes and liver impairments which were common but not serious. Anti-SSA and/or anti-SSB were the most related autoantibody. Most patients with NLE have relatively good prognosis.

[Effect of recombinant human tumor necrosis factor receptor type II-Fc fusion protein antibody on cytokines and bone metabolism in patients with juvenile idiopathic arthritis].

OBJECTIVE: To evaluate the influence of the recombinant human type II tumor necrosis factor receptor-antibody Fc fusion protein (rhTNFR:Fc) on cytokines and bone metabolism in patients with juvenile idiopathic arthritis (JIA). METHODS: This was a prospective, non-randomized, controlled and open-label study. Thirty-one patients with JIA in active state were enrolled at our hospital from December 2006 to June 2009. The mean age was 12.7 ± 2.3 years. Exclusive criteria included infection with tuberculosis and hepatitis B etc., abnormal renal or hepatic function. Study consists of two phases. During the first phase (0-3 months), according to the economic status, all JIA patients were divided into treatment and control groups. The treatment group consisted of 18 patients (enthesitis-related arthritis, n = 15; polyarticular-onset arthritis, n = 2; systemic-onset type, n = 1) on a regimen of rhTNFR:Fc 0.4 mg/kg, subcutaneously injected twice weekly. The control group contained 13 patients (enthesitis-related arthritis, n = 9; polyarticular-onset arthritis, n = 2; systemic-onset type, n = 2) on a regimen of MTX 10 mg × m(-2) × w(-1). Two intolerance patients were given sulfasalazine (SASP) 30-50 mg × kg(-1) × d(-1). During the second phase (3-6 months), the responding patients continued the original therapy. The rhTNFR:Fc group received a reduced dosage of 0.4 mg × kg(-1) × w(-1). All patients of both groups who became complicated with peripheral arthritis or were non-responding had the addition of SASP. Follow-up was conducted at baseline, 1 month, 3 months and 6 months. And TNF-α, MMP-3, IL-1ß, osteocalcin (BGP), ß-collagen fragment (ß-CTx), alkaline phosphatase, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and bone mineral density dynamic changes were examined respectively in the treatment process. RESULTS: Alkaline phosphatase and lumbar spine bone mineral density increased while TNF-α, IL-1ß, ESR and CRP decreased significantly in two groups (P < 0.05). ESR were 16 ± 8.0 mm/h vs 60 ± 38 mm/h, CRP 10 ± 7 mg/L vs 47 ± 37 mg/L and ß-CTx 2.1 ± 0.8 vs 1.1 ± 0.9 µg/L at 1 month in two groups respectively with statistic difference (P < 0.05). BGP increased and MMP-3 decreased in both groups with no statistic difference. Femur Ward's triangular area and forearm bone mineral density had no statistic difference between two groups. Interestingly, one case with bone fracture for two years has healed after a 6-month therapy of rhTNFR:Fc as proved by X-ray. CONCLUSION: Both rhTNFR:Fc and traditional DMARDs both can reduce the levels of TNF-α, IL-1ß, ESR and CRP and increase lumbar spine bone mineral density and ALP significantly. RhTNFR: Fc improves the acute phase index and bone metabolism index earlier than the traditional therapy. Thus disease and bone destruction are controlled more earlier.

[Efficacy comparison between transplanting microenvironmental induced and non-induced bone marrow mesenchymal stem cells in ischemic rat hearts].

OBJECTIVE: To compare the efficacy of transplanting bone marrow mesenchymal stem cell (BMSC) or microenvironmental induced BMSC (iBMSC) into the ischemic myocardium of rats with myocardial infarction. METHODS: iBMSC was defined as BMSC co-cultured with myocardial cells for 2 weeks. The stem cells or equal volume PBS were injected into ischemic border zone 1 wk after experimental infarction. Cardiac performance was evaluated at 1, 2, and 4 wk after cell transplantation by echocardiography and analyzed histologically at 4 wk after cell transplantations. RESULTS: Compared with PBS group, both BMSC and iBMSC transplantations reduced infarct size. iBMSC enhanced the beneficial effects of BMSC on improving cardiac function (FS: 28.5% +/- 4.3% in PBS, 29.0% +/- 2.0% in BMSC and 45.1% +/- 3.1% in iBMSC group at 4 weeks post transplantation, iBMSC group vs. PBS group P < 0.05, iBMSC group vs. BMSC group P < 0.05). Immunofluorescence microscopy results revealed co-localization of SPIO-labeled transplanted cells with cardiac markers for cardiomyocytes, indicating regeneration of damaged myocardium. CONCLUSION: Our data suggest that iBMSC implantation is more effective on improving cardiac function than BMSC implantation in this model. iBMSC might serve as a new promising therapeutic cell source for regenerating ischemic myocardium in patients with post-infarction heart failure.

[Clinical analysis of 79 pulmonary arterial hypertension cases from 1892 connective tissue disease patients].

OBJECTIVE: To understand the prevalence, investigate the correlation of clinical features, explore the early-stage diagnosis and treatment of pulmonary arterial hypertension (PAH) in patients with connective tissue disease (CTD). METHODS: All cases with pulmonary arterial hypertension in 1892 CTD patients were analyzed retrospectively. The risk factor of PAH was evaluated and the prognostic influence of different treatments and primary diseases analyzed. RESULTS: The prevalence of PAH in patients with connective tissue disease was about 4.2%(79/1892). In these patients, systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) had the highest incidence of PAH (18.18% and 12.00%) (P < 0.01). It was obviously higher than polymyositis/dermatomyositis (6.2%), systemic lupus erythematosus (4.4%), Sjogren syndrome (3.8%), rheumatoid arthritis (0.8%) and anti-phospholipid syndrome (0.5%), etc. (P < 0.01). Raynaud's phenomenon was related to a higher pulmonary arterial pressure (P < 0.01). There was a positive correlation (P < 0.01) between the presence of Raynaud's phenomenon and pulmonary arterial pressure. Abnormal lung function was a common finding. There were associations (P < 0.05) between the degree of pulmonary hypertension and IgG, anti-U1RNP antibody positive, antiphospholipid antibody positive, pericardial effusion and interstitial pneumonia. CONCLUSION: PAH is common in connective tissue disease. SSc and MCTD have the highest prevalence of PAH. The presence of Raynaud's phenomenon anti-U1RNP antibody is positively correlated with pulmonary arterial pressure. It can predict the development of PAH. It is useful to perform ultraechocardiogrphy for an early-stage diagnosis and prognostic analysis.

[Combined mesenchymal stem cells and allogenic bone marrow transplantation in treatment of MRL/lpr mice].

OBJECTIVE: In order to study the role of the bone marrow-derived mesenchymal stem cells (MSCs) transplanted with or without bone marrow (BM) in the treatment of lupus mice and the effect of MSCs in the onset of systemic lupus erythematosus (SLE). METHOD: Twenty 12-week-old female MRL/lpr mice were randomly divided into four groups, including simple bone marrow transplantation group (SG, BM 1 x 10(7)), united group-1 (UG1, BM 1 x 10(7) + MSCs 1 x 10(4)), united group-2 (UG2, BM 1 x 10(7) + MSCs 1 x 10()6), the positive control group (PG, no transplantation). BALB/c mice were used as the negative control group (NG, no transplantation). MSCs which were amplified from the bone marrow of male BALB/c mice in vitro were transplanted into the female MRL/lpr mice with or without BM. One month later Y chromosome was detected to confirm if the transplantation was successful or not. The change of weight, white blood cells, urine protein, anti-dsDNA antibody, the pathology and immunofluorescence of renal were observed to evaluate the therapeutic efficacy. RESULTS: Y chromosome was detected in all transplanted female mice. Compared with PG, urine protein concentration in SG, UG1 and UG2 significantly decreased 30 days after transplantation (P < 0.05). 40 days after transplantation, the tite of anti-dsDNA antibodies in SG (0.91 +/- 0.27) was still higher than NG, which OD value was 0.47 +/- 0.10 (P < 0.05), but there was no statistical difference among UG1 (0.76 +/- 0.28), UG2 (0.73 +/- 0.10) and NG (P > 0.05). However, 50 days after transplantation, there was no marked difference of the tite of anti-dsDNA antibodies in SG (0.55 +/- 0.15), UG1 (0.57 +/- 0.14) and UG2 (0.58 +/- 0.05) compared with NG (P > 0.05). After transplantation there was no vasculitis, no inflammatory cell infiltration in matrix and no obvious intercapillary cells proliferation in the kidney. The immunofluorescence became negative or weakly positive. CONCLUSION: MSCs transplantation with or without BM can both improve the pathogenetic condition of MRL/lpr mice. MSCs can accelerate the clearance of anti-dsDNA antibody and promote the restoration of injured organs. We presume that MSCs are important immunological regulation cells in SLE.

[An exploratory study on in vitro effects and mechanism of leflunomide on dendritic cells of systemic lupus erythematosus].

OBJECTIVE: To detect the effects of leflunomide to phenotype and function of dendritic cells (DCs) in systemic lupus erythematosus (SLE) patients, reveal the effective mechanism inducing remission of SLE and lay a research foundation for using 'inhibit' DCs to treat SLE in future. METHODS: The monocytes were isolated from peripheral blood of SLE patients and cultivated into DCs with cytokines such as GM-CSF and IL-4. A771726 (active metabolite) was added in with cytokines in leflunomide group, but not in control. DCs were harvested after 9 days culture. CD(80), CD(83), CD(86) and HLA-DR surface markers on DCs were detected by flow cytometry (FACS). The ability of DCs stimulating lymphocytes proliferation was detected by MTT assay. IL-10 and IFNgamma level in the supernatant of MLR were detected by ELISA and T cell subtype after MLR was detected by FACS. RESULTS: The DCs treated with A771726 showed a lower percentage expression of CD(83), CD(86) and HLA-DR phenotype (CD(83): 72.70 +/- 1.77 vs. 79.36 +/- 4.80, CD(86): 63.50 +/- 14.06 vs. 83.91 +/- 9.81, HLA-DR: 80.44 +/- 12.56 vs. 90.51 +/- 8.63, all P < 0.01), a weaker ability to stimulating T lymphocytes proliferation (at DC:TC = 1:10, 0.285 +/- 0.079 vs. 0.458 +/- 0.100; at DC:TC = 1:50, 0.194 +/- 0.054 vs. 0.382 +/- 0.023, all P < 0.01) and a lower secretive level of IL-10 in the MLR supernatant [(195.0 +/- 36.9) microg/L vs. (423.6 +/- 93.2) microg/L, P < 0.01], exclude those it could still increase amount of a new T cell subtype--CD(4)(+)CD(25)(+)CTLA(4)(+) T cell (12.00% & 6.23%). CONCLUSIONS: A771726 can inhibit DCs maturation, the immature DCs can inhibit T cells proliferation and refrain T cells from dividing into Th(2) subtype, and also the immature DCs can induce a sort of regulate T cell (CD(4)(+)CD(25)(+)CTLA(4)(+) T cell) production. Through that LEF may correct part over humor immune dysfunction and get a new immune balance in SLE.

IL-17 induces autoantibody overproduction and peripheral blood mononuclear cell overexpression of IL-6 in lupus nephritis patients.

OBJECTIVE: To investigate the role of IL-17 in the overproduction of autoantibodies and IL-6 overexpression by peripheral blood mononuclear cells (PBMC) of lupus nephritis (LN) patients. METHODS: Fifteen consecutively hospitalized LN patients were selected as subjects and 15 healthy adults as normal controls. PBMC were obtained by Ficoll density gradient centrifugation. IgG, anti-dsDNA antibody and IL-6 protein levels were assessed using enzyme-linked immunosorbent assays (ELISA) on the supernatant of cultured PBMC of LN patients or normal controls. IL-6 mRNA levels in PBMC were measured using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In medium culture, IgG, anti-dsDNA and IL-6 protein levels of the supernatant of PBMC from LN patients were significantly higher than those from normal controls (1492.1 +/- 73.2 ng/ml vs 636.7 +/- 51.9 ng/ml for IgG, 306.6 +/- 53.7 IU/ml vs 95.8 +/- 11.6 IU/ml for anti-dsDNA and 50.92 +/- 15.92 ng/ml vs 1.77 +/- 0.73 ng/ml for IL-6, all P < 0.001). In LN patients, IgG, anti-dsDNA and IL-6 protein levels were higher in the supernatants of PBMC in the IL-17-stimulated culture than the medium culture, but in normal controls, only the IL-6 protein levels were significantly higher. The increase in IgG, anti-dsDNA and IL-6 protein levels induced by IL-17 was dose-dependent and could be completely blocked by IL-17 monoclonal antibody mIgG(28) and partially blocked by dexamethasone. Similarly, IL-6 mRNA overexpression of PBMC in LN patients or normal controls induced by IL-17 was both dose- and time-dependent. During medium culture, IL-6 mRNA levels in LN patients were significantly higher than those in normal controls (1.80 +/- 0.11 vs 0.36 +/- 0.07). During stimulation with IL-17, IL-6 mRNA levels in LN patients were higher than those in normal controls (3.21 +/- 0.24 vs 1.30 +/- 0.14, P < 0.05) and also significantly higher when comparing the stimulated culture with the medium culture either in LN patients or normal control. CONCLUSIONS: IL-17 may play an important role in the pathogenesis of LN through the induction of IgG, anti-dsDNA overproduction and IL-6 overexpression of PBMC in LN patients.