scholarly journals 1,25-dihydroxyvitamin D3 Ameliorates Lupus Nephritis Through Inhibiting NF-κB and MAPKs Signaling Pathways in MRL/lpr Mice

2021 ◽  
Author(s):  
Xuewei Li ◽  
Yingzhe Zhao ◽  
Ning Xu ◽  
E Lv ◽  
Cunzeng Ci ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Signaling Pathways ◽  
Intraperitoneal Injection ◽  
Underlying Mechanism ◽  
Skin Lesions ◽  
Treated Group ◽  
Control Group ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Tnf Α

Abstract Background: Lupus nephritis (LN) is a common and serious complication of systemic lupus erythematosus (SLE). However, the etiology and pathogenesis of LN remain unknown. 1,25-dihydroxyvitamin D3（1,25-(OH)2-VitD3）is the active form of vitamin D, which has been known to have important functions in inflammation and immune diseases. In this study, we investigated Its protective effects and underlying mechanism in MRL/lpr mice, a well-studied animal model for lupus.Methods: At the age of 11 weeks, forty-eight MRL/lpr mice were randomly divided into two groups with 24 mice per group: the VitD3-treated group and control group. Mice in the VitD3-treated group received 4μg/kg 1,25-dihydroxyvitamin D3 in 1％ dimethyl sulfoxide (DMSO) intraperitoneal injection twice a week for 3 weeks (mice were executed at 0,2,4,6 weeks after treatment); mice in the control group treated with intraperitoneal injection of 1% DMSO for 3 weeks (mice were executed at 0,2,4,6 weeks after injections). The mice were sacrificed and the serum and kidney samples were collected respectively at planned intervals. Then the skin lesions, histological changes, inflammatory factors (TNF-α, IL-17) and immunological markers (A-ds DNA, C3, IgG, IgM) with time were analyzed between the groups. Furthermore, the NF-κB and MAPKs signaling pathways were also detected to explicate the underlying mechanism. Results: Compared to the control group, mice in the VitD3-treated group showed less skin lesions, less kidney injury, lower serum anti-ds DNA antibody, lower inflammatory cytokines TNF-α, IL-17 and higher serum complement C3; they also had less deposition of IgG, IgM and C3 within glomeruli. Moreover, the expressions of NF-κB and MAPKs signaling pathways were decreased, while those levels were increased with time.Conclusion: This study shows that 1,25-dihydroxyvitamin D3 exerts a protective effect against lupus nephritis via regulating the NF-κB and MAPKs signaling pathways, which will be developed as a potential agent for the treatment of Lupus nephritis. And the relationship between lupus activity and NF-kB and MAPKs signaling pathways with time was revealed.

scholarly journals Inhibition of Leukocyte Entry into the Brain by the Selectin Blocker Fucoidin Decreases Interleukin-1 (IL-1) Levels but Increases IL-8 Levels in Cerebrospinal Fluid during Experimental Pneumococcal Meningitis in Rabbits

2000 ◽  
Vol 68 (6) ◽  
pp. 3153-3157 ◽  
Author(s):  
Christian Østergaard ◽  
Runa Vavia Yieng-Kow ◽  
Thomas Benfield ◽  
Niels Frimodt-Møller ◽  
Frank Espersen ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Pneumococcal Meningitis ◽  
Interleukin 1 ◽  
Treated Group ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Significant Difference ◽  
The Brain ◽  
Experimental Pneumococcal Meningitis

ABSTRACT The polysaccharide fucoidin is a selectin blocker that inhibits leukocyte recruitment into the cerebrospinal fluid (CSF) during experimental pneumococcal meningitis. In the present study, the effect of fucoidin treatment on the release of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), and IL-8 into the CSF was investigated. Rabbits (n = 7) were treated intravenously with 10 mg of fucoidin/kg of body weight every second hour starting 4 h after intracisternal inoculation of ∼106 CFU of Streptococcus pneumoniae type 3 (untreated control group, n = 7). CSF samples were obtained every second hour during a 16-h study period. Treatment with fucoidin caused a consistent and significant decrease in CSF IL-1 levels (in picograms per milliliter) between 12 and 16 h (0 versus 170, 0 versus 526, and 60 versus 1,467, respectively;P < 0.02). A less consistent decrease in CSF TNF-α levels was observed in the fucoidin-treated group, but with no significant difference between the two groups (P > 0.05). In contrast, there was no attenuation in CSF IL-8 levels. Indeed, there was a significant increase in CSF IL-8 levels (in picograms per milliliter) in the fucoidin-treated group at 10 and 12 h (921 versus 574 and 1,397 versus 569, respectively;P < 0.09). In conclusion, our results suggest that blood-derived leukocytes mainly are responsible for the release of IL-1 and to some degree TNF-α into the CSF during pneumococcal meningitis, whereas IL-8 may be produced by local cells within the brain.

scholarly journals EKSPRESI Tumor Necrosis Factor alpha (TNF-α) DAN Transforming growth factors beta (TGF-β) PADA PERIODONTITIS APIKALIS KRONIS AKIBAT INDUKSI Enterococcus faecalis PADA TIKUS WISTAR

2019 ◽  
Vol 7 (2) ◽  
pp. 66
Author(s):  
Richard Fritzgerald ◽  
Cecilia Lunardhi ◽  
Ruslan Effendy ◽  
Tamara Yuanita
Keyword(s):  
Tissue Damage ◽  
Treated Group ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Transforming Growth Factors ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Background. Root canal treatment is a main role in decreasing infection from root canal and pulp. The main cause of periapical damage mostly are bacteries. E.faecalis is a bactery that is found as an etiology of endodontic treatment failure. Cell wall of this bacteria is containing Lipoteichoic acid (LTA). LTA can penetrate into the periradicular tissue, act as endotoxin in host and cause periradicular inflammation then lead to bone destruction. LTA stimulates immunology reaction that produce Tumor Necrosis Factor alpha (TNF-α) and Transforming growth factors beta (TGF-ß). TNF-α is a main mediator and also have an important role in inflamation response otherwise TGF-ß is working as a multifunction  regulator of cell growth and differentiation during reforming and remodelling.  Purpose. The aim of this study is to know about the expression of TNF-α and TGF-ß during the periapical tissue damage due to induction of E.faecalis. Method. This study used laboratory experimental with the post test only control group design. A total of 30 male rats were randomly divided into 3 main groups, Group A (control negative) : normal tooth. Group B (control positive) : every tooth was induced only by sterile BHI-b. Group C (treated group) : every tooth  was induced by 10 μl BHI-b E.faecalis ATCC212(106 CFU). The animals were sacrificed 21 days later and prepared for histological examination of tissue damage, then we did the immunohistochemistry  followed by calculation on the light microscope. Result. The analysis revealed that the expression of TNF-α at treated group are higher than negative control and positive control but the expression of  TGF-ß at treated group are higher than the negative control group but lower than positive control. Conclusion. From this study we know that the expression of TNF-α and TGF-ß are changing during the periapical tissue damage that induced by E.faecalis.

scholarly journals Expression Profiling of Circular RNAs and Micrornas in Heart Tissue of Mice with Alcoholic Cardiomyopathy

2018 ◽  
Vol 46 (6) ◽  
pp. 2284-2296 ◽  
Author(s):  
Yuqiao Yang ◽  
Hongmei Chen ◽  
Nina Ding ◽  
Shuo Wang ◽  
Zhantao Duan ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Signaling Pathways ◽  
Treated Group ◽  
Heart Tissue ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Control Group ◽  
Alcoholic Cardiomyopathy ◽  
Bioinformatics Software ◽  
Heavy Alcohol Consumption

Background/Aims: Chronic heavy alcohol consumption may result in alcoholic cardiomyopathy. This study was designed to screen differentially expressed microRNAs and circular RNAs in heart tissue of mice with alcoholic cardiomyopathy to reveal the underlying molecular mechanism. Methods: Having established a murine alcoholic cardiomyopathy model, we screened differentially expressed microRNAs and circular RNAs in three heart samples from the alcohol-treated and control groups by high-throughput microarray analysis. We analyzed the function and biological signaling pathways of differentially expressed non-coding RNAs closely related to alcoholic cardiomyopathy using bioinformatics software to identify some mRNAs and their biological signaling pathways closely related to alcoholic cardiomyopathy. Results: Nineteen microRNAs and 265 circular RNAs were differentially expressed in the alcohol-treated group compared with the control group. After analyzing gene function and signaling pathways by bioinformatics software, we found that the differentially expressed mRNAs were associated with carbohydrate metabolism. Conclusions: Chronic alcohol consumption can change the non-coding RNA profile of heart tissue, which is closely related to the pathological mechanisms of alcoholic cardiomyopathy.

T-614 inhibits human aortic adventitial fibroblast proliferation and promotes interleukin-8 production in vitro

Vascular ◽  
2019 ◽  
Vol 28 (3) ◽  
pp. 314-320
Author(s):  
Weiping Ci ◽  
Tian Wang ◽  
Taotao Li ◽  
Jin Wan
Keyword(s):  
Cell Viability ◽  
Vascular Wall ◽  
Underlying Mechanism ◽  
Interleukin 8 ◽  
Control Group ◽  
Survival Fraction ◽  
Tnf Α ◽  
Significant Difference ◽  
Factor Α

Objectives The effect and underlying mechanism of T-614 (iguratimod) on Takayasu’s arteritis (TA) are unknown. Here, we report the effects of T-614 on cell proliferation and interleukin-8 (IL-8) production in human aortic adventitial fibroblasts (HAAFs) in vitro and explore its initial benefit in terms of vascular wall inflammation and remodeling for patients with TA. Methods HAAFs were cultured with 0, 5, 50, 100, or 250 μg/ml T-614 in the absence or presence of tumor necrosis factor-α (TNF-α) in vitro. Cell viability was determined by a modified MTT assay. Supernatant IL-8 levels were measured by enzyme-linked immunosorbent assays. Results In the presence of TNF-α, compared to that in the control group, cell viability of HAAFs significantly decreased in the 50, 100, and 250 μg/ml T-614 treatment groups (OD value: P <  0.01, P <  0.001, P <  0.001, respectively; survival fraction (SF): P <  0.05, P <  0.001, P <  0.001, respectively). However, there was no significant difference in cell viability between TNF-α-stimulated and unstimulated groups at the same concentration of T-614. In the absence or presence of TNF-α, T-614 suppressed HAAF cell viability dose-dependently (OD value: r = −0.915, P =  0.000; r = −0.926, P =  0.000, respectively; SF: r = −0.897, P =  0.000; r = −0.885, P =  0.000, respectively). Compared to that in the control group, in the absence of TNF-α, IL-8 levels in the 5 and 100 μg/ml T-614-treated groups were significantly higher ( P <  0.05); in the presence of TNF-α, IL-8 levels in the 5, 50, and 100 μg/ml T-614-treated groups were significantly higher ( P <  0.001, P <  0.001, P <  0.01, respectively). Further, there was a negative correlation between supernatant IL-8 levels and T-614 concentration in groups stimulated with TNF-α ( r = −0.670, P =  0.000), but there was no significant correlation between these parameters in groups that were not stimulated with TNF-α. Conclusions In the absence or presence of TNF-α, T-614 can inhibit HAAF proliferation and promote IL-8 production in vitro; therefore, it could be used to prevent adventitial thickening of the aorta and improve vascular remodeling in inflammatory environments in vitro and might provide a new immunotherapeutic intervention for TA.

scholarly journals Anti-Inflammatory Property of the Essential Oil from Cinnamomum camphora (Linn.) Presl Leaves and the Evaluation of Its Underlying Mechanism by Using Metabolomics Analysis

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4796
Author(s):  
Jiali Chen ◽  
Cailin Tang ◽  
Yang Zhou ◽  
Rongfei Zhang ◽  
Shaoxia Ye ◽  
...  
Keyword(s):  
Essential Oil ◽  
Mrna Expression ◽  
Underlying Mechanism ◽  
Treated Group ◽  
Microglial Cells ◽  
Cinnamomum Camphora ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Bv2 Microglial Cells

Cinnamomum camphora (Linn.) Presl has been widely used in traditional Chinese medicine for a variety of purposes. Our previous study indicated the antibacterial mechanism of the essential oil (EO) from C. camphora leaves; however, its anti-inflammatory activity and the underlying mechanism have not been clearly demonstrated. Thus, the present study investigated its anti-inflammatory property. Our data revealed that EO significantly decreased the release of nitric oxide (NO) and the mRNA expression of inducible NO synthase (iNOS) in lipopolysaccharide (LPS)-induced BV2 microglial cells. EO also attenuated LPS-induced increase in the mRNA expression and secretion of inflammatory cytokines including interleukin-6 (IL-6), IL-18, IL-1β and tumor necrosis factor-α (TNF-α). Furthermore, the metabolic profiles of LPS-induced BV2 microglial cells treated with or without EO were explored. Thirty-nine metabolites were identified with significantly different contents, including 21 upregulated and 18 downregulated ones. Five pathways were enriched by shared differential metabolites. Compared with the control cells, the glucose level was decreased, while the lactate level was increased, in the culture supernatant from LPS-stimulated cells, which were reversed by EO treatment. Moreover, compared to the LPS-treated group, the activities of phosphofructokinase (PFK) and pyruvate kinase (PK) in EO group were decreased. In summary, the current study demonstrated that EO from C. camphora leaves acts as an anti-inflammatory agent, which might be mediated through attenuating the glycolysis capacity of microglial cells.

scholarly journals Blockade of NF-κB and MAPK pathways by ulinastatin attenuates wear particle-stimulated osteoclast differentiation in vitro and in vivo

2016 ◽  
Vol 36 (5) ◽  
Author(s):  
Jiang-Ying Ru ◽  
Hai-Dong Xu ◽  
Dai Shi ◽  
Jun-Bo Pan ◽  
Xiao-Jin Pan ◽  
...  
Keyword(s):  
Cathepsin K ◽  
Treated Group ◽  
Receptor Activation ◽  
Raw264.7 Cells ◽  
Control Group ◽  
Nuclear Factor ◽  
Trabecular Thickness ◽  
Tnf Α

Ulinastatin, a urinary trypsin inhibitor (UTI), is widely used to clinically treat lipopolysaccharide (LPS)-related inflammatory disorders recently. Adherent pathogen-associated molecular patterns (PAMPs), of which LPS is the best-studied and classical endotoxin produced by Gram-negative bacteria, act to increase the biological activity of osteopedic wear particles such as polymethyl-methacrylate (PMMA) and titanium particles in cell culture and animal models of implant loosening. The present study was designed to explore the inhibitory effect of UTI on osteoclastogenesis and inflammatory osteolysis in LPS/PMMA-mediated Raw264.7 cells and murine osteolysis models, and investigate the potential mechanism. The in vitro study was divided into the control group, LPS-induced group, PMMA-stimulated group and UTI-pretreated group. UTI (500 or 5000 units/ml) pretreatment was followed by PMMA (0.5 mg/ml) with adherent LPS. The levels of inflammatory mediators including tumour necrosis factor-α (TNF-α), matrixmetallo-proteinases-9 (MMP-9) and interleukin-6 (IL-6), receptor activation of nuclear factor NF-κB (RANK), and cathepsin K were examined and the amounts of phosphorylated I-κB, MEK, JNK and p38 were measured. In vivo study, murine osteolysis models were divided into the control group, PMMA-induced group and UTI-treated group. UTI (500 or 5000 units/kg per day) was injected intraperitoneally followed by PMMA suspension with adherent LPS (2×108 particles/25 μl) in the UTI-treated group. The thickness of interfacial membrane and the number of infiltrated inflammatory cells around the implants were assessed, and bone mineral density (BMD), trabecular number (Tb.N.), trabecular thickness (Tb.Th.), trabecular separation (Tb.Sp.), relative bone volume over total volume (BV/TV) of distal femur around the implants were calculated. Our results showed that UTI pretreatment suppressed the secretion of proinflammatory cytokines including MMP-9, IL-6, TNF-α, RANK and cathepsin K through down-regulating the activity of nuclear factor kappa B (NF-κB) and MAPKs partly in LPS/PMMA-mediated Raw264.7 cells. Finally, UTI treatment decreased the inflammatory osteolysis reaction in PMMA-induced murine osteolysis models. In conclusion, these results confirm the anti-inflammatory potential of UTI in the prevention of particle disease.

scholarly journals Pleiotropic effects of the steroid hormone 1,25-dihydroxyvitamin D3 on the recruitment of mesenchymal lineage progenitors in fetal rat calvaria cell populations

2006 ◽  
Vol 36 (3) ◽  
pp. 425-433 ◽  
Author(s):  
Shulin Zhang ◽  
Melinda Chan ◽  
Jane E Aubin
Keyword(s):  
Single Cell ◽  
Steroid Hormone ◽  
Cell Populations ◽  
Control Group ◽  
Dihydroxyvitamin D3 ◽  
Mesenchymal Progenitors ◽  
1,25 Dihydroxyvitamin D3 ◽  
Rat Calvaria ◽  
Neural Markers

The steroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits osteogenesis while stimulating adipogenesis in vitro. We hypothesized that 1,25(OH)2D3 redirects the fate of osteoblast/adipocyte bipotential progenitors and other potential progenitors towards adipogenesis, a process possibly underlying the pathogenesis of osteopenic diseases such as osteoporosis. We therefore tested the global effects of 1,25(OH)2D3 on the recruitment of mesenchymal progenitors including osteogenic, chondrogenic, adipogenic and myogenic lineages (colony forming cell (CFC)-osteoblast (CFC-O), CFC-chondrocyte (CFC-C), CFC-adipocyte (CFC-A), and CFC-myoblast (CFC-M) respectively) in rat calvaria (RC) cell populations using gene expression profiling of single cell-derived colonies. Based on expression of lineage specific transcripts, 86% of single cell-derived colonies in untreated cultures simultaneously co-expressed transcripts of two, three, or four of the mesenchymal lineages tested. The distribution of mesenchymal progenitors in 1,25(OH)2D3-treated cultures was significantly changed compared with the control group, i.e. CFC-O were reduced (from 6 to 0%) and CFC-O/A bipotential (0 to 8.2%), CFC-C (4 to 10.2%) and CFC-Fibroblast (CFC-F) (4 to 16%) were increased. 1,25(OH)2D3 did not affect the frequency of tri- or tetra-lineage colonies. Single lineage CFC-A colonies were not detected in either the control or 1,25(OH)2D3 treatment group under the conditions tested.Since the parietal bones used for cell isolation derive from neuroectoderm, we also analyzed for expression of the neural markers nestin and β3 tubulin in these colonies. Surprisingly, 90% (45 of 50) of the colonies in the control group expressed neural markers, a frequency not changed by 1,25(OH)2D3 treatment. The current studies demonstrate the global and developmental stage-specific effects of 1,25(OH)2D3 on mesenchymal lineage progenitors, and suggest that the effects of 1,25(OH)2D3 on osteogenesis and adipogenesis in RC populations are mediated, at least in part, by increased recruitment of CFC-O/A, but not CFC-A type precursors.

scholarly journals Plasma BDNF and Cytokines Correlated with Protein Biomarkers for Bipolar II Disorder

2021 ◽  
Vol 11 (12) ◽  
pp. 1282
Author(s):  
Sheng-Yu Lee ◽  
Tzu-Yun Wang ◽  
Ru-Band Lu ◽  
Liang-Jen Wang ◽  
Cheng-Ho Chang ◽  
...  
Keyword(s):  
Underlying Mechanism ◽  
Trna Synthetase ◽  
Inflammatory Factors ◽  
Control Group ◽  
Protein Biomarkers ◽  
Bdnf Level ◽  
Bipolar Ii Disorder ◽  
Bipolar Ii ◽  
Tnf Α ◽  
Factor Α

We have previously identified five candidate proteins (matrix metallopeptidase 9 (MMP9), phenylalanyl-TRNA synthetase subunit beta (FARSB), peroxiredoxin 2 (PRDX2), carbonic anhydrase 1 (CA-1), and proprotein convertase subtilisin/kexin Type 9 (PCSK9)) as potential biomarkers for bipolar II disorder (BD-II). These candidate proteins have been associated with neuroprotective factors (BDNF) and inflammatory factors (cytokines, C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α)). However, the correlations between these proteins with plasma BDNF and inflammatory factors remain unknown. We recruited a total of 185 patients with BD-II and 186 healthy controls. Plasma levels of candidate proteins, BDNF, cytokines (TNF-α, CRP, and interleukin-8 (IL-8)) were assessed from each participant. The correlations between levels of candidate proteins, BDNF, and cytokines were analyzed. In the BD-II group, we found that the level of FARSB was positively correlated with the BDNF level (r = 0.397, p < 0.001) and IL-8 (r = 0.320, p < 0.001). The CA-1 level positively correlated with IL-8 (r = 0.318, p < 0.001). In the control group, we found that the FARSB level positively correlated with the BDNF level (r = 0.648, p < 0.001). The CA-1 level positively correlated with TNF-α (r = 0.231, p = 0.002), while the MMP-9 level positively correlated with the CRP level (r = 0.227, p = 0.002). Our results may help in clarifying the underlying mechanism of these candidate proteins for BD-II.

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