Dopamine attenuates lipopolysaccharide-induced expression of proinflammatory cytokines by inhibiting the nuclear translocation of NF-κB p65 through the formation of dopamine quinone in microglia.

2020 ◽  
Vol 866 ◽  
pp. 172826 ◽  
Author(s):  
Yasuhiro Yoshioka ◽  
Yuta Sugino ◽  
Fumiya Shibagaki ◽  
Akiko Yamamuro ◽  
Yuki Ishimaru ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Nuclear Translocation ◽  
Induced Expression ◽  
Dopamine Quinone

Plasminogen activator inhibitor-1 potentiates LPS-induced neutrophil activation through a JNK–mediated pathway

2006 ◽  
Vol 95 (05) ◽  
pp. 829-835 ◽  
Author(s):  
Sang-Hyun Kwak ◽  
Xue-Qing Wang ◽  
Qianbin He ◽  
Wen-Feng Fang ◽  
Sanchayita Mitra ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Proinflammatory Cytokines ◽  
Nuclear Translocation ◽  
Plasminogen Activator Inhibitor ◽  
Neutrophil Activation ◽  
Plasminogen Activator Inhibitor 1 ◽  
Inflammatory Conditions ◽  
Jnk Activation ◽  
Activator Inhibitor ◽  
Pai 1

SummaryPlasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor superfamily, modulates fibrinolysis by interacting with proteolytic mediators, including urokinase plasminogen activator (uPA). Although the roles of uPA and PAI-1 in plasmin generation and the degradation of fibrin are well known, recent evidence also suggests that they can participate in acute inflammatory conditions that involve neutrophil activation. In the present experiments, we found that the addition of PAI-1 to LPS-stimulated neutrophils resulted in enhanced nuclear translocation of NF-κB and increased production of the proinflammatory cytokines IL-1β,Tnf-α,and Mip-2.uPA and the kringle domain (KD) of uPA potentiated cytokine expression and NF-κB activation by neutrophils cultured with LPS, and had additive effects when combined with PAI-1. The c-Jun N-terminal kinase (JNK) was activated after exposure of resting neutrophils to PAI-1 or the uPA KD. Enhanced JNK activation, but not that of other kinases induced by LPS, was present in neutrophils cocultured with PAI-1 or uPA KD. Inhibition of JNK activation prevented the potentiation of expression of proinflammatory cytokines induced by PAI-1 or uPA KD in LPS stimulated neutrophils. These results demonstrate that PAI-1 and uPA KD enhance LPSinduced neutrophil responses through their effects on JNK mediated pathways.

scholarly journals Carbon Monoxide Inhibits Tenascin-C Mediated Inflammation via IL-10 Expression in a Septic Mouse Model

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Md. Jamal Uddin ◽  
Chun-shi Li ◽  
Yeonsoo Joe ◽  
Yingqing Chen ◽  
Qinggao Zhang ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Proinflammatory Cytokines ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Septic Mouse ◽  
Induced Expression ◽  
Tenascin C ◽  
Co Gas

Tenascin-C (TN-C), an extracellular matrix (ECM) glycoprotein, is specifically induced upon tissue injury and infection and during septic conditions. Carbon monoxide (CO) gas is known to exert various anti-inflammatory effects in various inflammatory diseases. However, the mechanisms underlying the effect of CO on TN-C-mediated inflammation are unknown. In the present study, we found that treatment with LPS significantly enhanced TN-C expression in macrophages. CO gas, or treatment with the CO-donor compound, CORM-2, dramatically reduced LPS-induced expression of TN-C and proinflammatory cytokines while significantly increased the expression of IL-10. Treatment with TN-C siRNA significantly suppressed the effects of LPS on proinflammatory cytokines production. TN-C siRNA did not affect the CORM-2-dependent increase of IL-10 expression. In cells transfected with IL-10 siRNA, CORM-2 had no effect on the LPS-induced expression of TN-C and its downstream cytokines. These data suggest that IL-10 mediates the inhibitory effect of CO on TN-C and the downstream production of proinflammatory cytokines. Additionally, administration of CORM-2 dramatically reduced LPS-induced TN-C and proinflammatory cytokines production while expression of IL-10 was significantly increased. In conclusion, CO regulated IL-10 expression and thus inhibited TN-C-mediated inflammationin vitroandin vivo.

scholarly journals Cell‐Penetrating MK2 Inhibitory Peptide Blocks LPS‐Induced Expression of Proinflammatory Cytokines in HepG2 Hepatocytes

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Paul Kim ◽  
Tiffany Francis ◽  
Durina Dalrymple ◽  
Yaswanthi Yanamadala ◽  
Victor M. Carriere ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Inhibitory Peptide ◽  
Induced Expression ◽  
Cell Penetrating

scholarly journals PPARα Agonist Suppresses Inflammation after Corneal Alkali Burn by Suppressing Proinflammatory Cytokines, MCP-1, and Nuclear Translocation of NF-κB

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 114 ◽  
Author(s):  
Yuichiro Nakano ◽  
Masaaki Uchiyama ◽  
Takeshi Arima ◽  
Shinya Nagasaka ◽  
Tsutomu Igarashi ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Nuclear Translocation ◽  
Vehicle Group ◽  
Peroxisome Proliferator ◽  
Corneal Tissue ◽  
Mrna Levels ◽  
Basal Cells ◽  
Monocyte Chemoattractant Protein 1 ◽  
Corneal Injury ◽  
Pparα Agonist

We investigated the effect of a peroxisome proliferator-activated receptor α (PPARα) agonist after corneal alkali injury. Fenofibrate 0.05% (PPARα agonist group) or vehicle (Vehicle group) was topically instilled onto the rat cornea after injury. Histological, immunohistochemical, and real-time reverse transcription PCR analyses were performed. PPARα-positive cells were observed among basal cells of the corneal epithelium in normal and alkali-burned corneas. The number of infiltrating neutrophils and macrophages at the corneal limbus was lower in the PPARα agonist group. Interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor-An mRNA expression was suppressed in the PPARα agonist group compared to the Vehicle group. mRNA levels of nuclear factor kappa B (NF-κB) in corneal tissue were not different. However, NF-κB was expressed in the cytoplasm of basal cells in the PPARα agonist group and in the nucleus in the Vehicle group. MCP-1 was more weakly expressed in the PPARα agonist group. The PPARα agonist inhibited inflammation during the early phase after injury. Anti-inflammatory effects of the PPARα agonist included prevention of up-regulation of proinflammatory cytokines and MCP-1, and prevention of inflammatory cell infiltration into the injured cornea. Thus, a PPARα agonist may be a promising treatment for corneal injury.

scholarly journals Dehydrocorydaline Accounts the Majority of Anti-Inflammatory Property of Corydalis Rhizoma in Cultured Macrophage

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xiangpeng Kong ◽  
Zhicong Chen ◽  
Yingjie Xia ◽  
Etta Y. L. Liu ◽  
Haiqin Ren ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Proinflammatory Cytokines ◽  
Blood Circulation ◽  
Nuclear Translocation ◽  
Total Alkaloids ◽  
Tnf Α ◽  
Different Types ◽  
Anti Inflammatory ◽  
Chromatographic Peaks

Corydalis Rhizoma (CR) is a commonly used traditional Chinese medicine for its potency in activating blood circulation and analgesia. In clinic, CR extracts or components are commonly used in the treatment of myocardial ischemia, rheumatism, and dysmenorrhea with different types of inflammation. However, due to different mechanism of pain and inflammation, the anti-inflammatory property of CR has not been fully revealed. Here, the major chromatographic peaks of CR extracts in different extracting solvents were identified, and the anti-inflammatory activities of CR extracts and its major alkaloids were evaluated in LPS-treated macrophages by determining expressions of proinflammatory cytokines, IκBα and NF-κB. The most abundant alkaloid in CR extract was dehydrocorydaline, having >50% of total alkaloids. Besides, the anti-inflammatory activities of dehydrocorydaline and its related analogues were demonstrated. The anti-inflammatory roles were revealed in LPS-treated cultured macrophages, including (i) inhibiting proinflammatory cytokines release, for example, TNF-α, IL-6; (ii) suppressing mRNA expressions of proinflammatory cytokines; (iii) promoting IκBα expression and suppressing activation of NF-κB transcriptional element; and (iv) reducing the nuclear translocation of NF-κB. The results supported that dehydrocorydaline was the major alkaloid in CR extract, which, together with its analogous, accounted the anti-inflammatory property of CR.

scholarly journals Allicin Alleviates Dextran Sodium Sulfate- (DSS-) Induced Ulcerative Colitis in BALB/c Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Ashok Kumar Pandurangan ◽  
Salmiah Ismail ◽  
Zeinab Saadatdoust ◽  
Norhaizan Mohd. Esa
Keyword(s):  
Body Weight ◽  
Proinflammatory Cytokines ◽  
Sodium Sulfate ◽  
Nuclear Translocation ◽  
Dextran Sodium Sulfate ◽  
Nuclear Accumulation ◽  
Mrna Levels ◽  
Inhibitory Protein ◽  
Reduced Body ◽  
Enzymic Antioxidants

The objective of this study is to evaluate the effect of allicin (10 mg/kg body weight, orally) in an experimental murine model of UC by administering 2.5% dextran sodium sulfate (DSS) in drinking water to BALB/c mice. DSS-induced mice presented reduced body weight, which was improved by allicin administration. We noted increases in CD68 expression, myeloperoxidase (MPO) activities, and Malonaldehyde (MDA) and mRNA levels of proinflammatory cytokines, such astumor necrosis factor- (TNF-)α, interleukin- (IL-) 1β, IL-6, andIL-17, and decrease in the activities of enzymic antioxidants such as superoxide dismutase (SOD), Catalase (CAT), Glutathione reductase (GR), and Glutathione peroxidase (GPx) in DSS-induced mice. However, allicin treatment significantly decreased CD68, MPO, MDA, and proinflammatory cytokines and increased the enzymic antioxidants significantly (P<0.05). In addition, allicin was capable of reducing the activation and nuclear accumulation of signal transducer and activator of transcription 3 (STAT3), thereby preventing degradation of the inhibitory protein IκB and inducing inhibition of the nuclear translocation of nuclear factor (NF)-κB-p65 in the colonic mucosa. These findings suggest that allicin exerts clinically useful anti-inflammatory effects mediated through the suppression of the NF-κB and IL-6/p-STAT3Y705pathways.

scholarly journals Overexpression of Phospholipid-hydroperoxide Glutathione Peroxidase in Human Dermal Fibroblasts Abrogates UVA Irradiation-induced Expression of Interstitial Collagenase/Matrix Metalloproteinase-1 by Suppression of Phosphatidylcholine Hydroperoxide-mediated NFκB Activation and Interleukin-6 Release

2004 ◽  
Vol 279 (44) ◽  
pp. 45634-45642 ◽  
Author(s):  
Jutta Wenk ◽  
Jutta Schüller ◽  
Christina Hinrichs ◽  
Tatjana Syrovets ◽  
Ninel Azoitei ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Matrix Metalloproteinase ◽  
Uv Irradiation ◽  
Interleukin 6 ◽  
Nuclear Translocation ◽  
Phospholipid Hydroperoxide Glutathione Peroxidase ◽  
Induced Expression ◽  
Uva Irradiation ◽  
Phospholipid Hydroperoxide ◽  
Matrix Metalloproteinase 1

Phospholipid-hydroperoxide glutathione peroxidase (PHGPx) exhibits high specific activity in reducing phosphatidylcholine hydroperoxides (PCOOHs) and thus may play a central role in protecting the skin against UV irradiation-triggered detrimental long term effects like cancer formation and premature skin aging. Here we addressed the role of PHGPx in the protection against UV irradiation-induced expression of matrix metalloproteinase-1 (MMP-1). For this purpose, we created human dermal fibroblast cell lines overexpressing human PHGPx. Overexpression led to a significant increase in PHGPx activity. In contrast to a maximal 4.5-fold induction of specific MMP-1 mRNA levels in vector-transfected cells at 24 h after UVA irradiation, no MMP-1 induction occurred at any studied time point after UVA treatment of PHGPx-overexpressing fibroblasts. As interleukin-6 (IL-6) was earlier shown to mediate the UVA induction of MMP-1, we studied whether PHGPx overexpression might interfere with the NFκB-mediated IL-6 induction and downstream signaling. Using transient transfections of IL-6 promoter constructs containing NFκB binding sites, we observed a high induction of the reporter gene luciferase in vector-transfected control cells and a significantly lower induction in PHGPx-overexpressing fibroblasts following UVA irradiation. Consistently both UVA irradiation and treatment of fibroblasts with PCOOHs led to phosphorylation and nuclear translocation of the p65 subunit, whereas cells overexpressing PHGPx exhibited impaired NFκB activation, p65 phosphorylation, and nuclear translocation. In line with this, the PHGPx-overexpressing fibroblasts showed a reduced constitutive and UVA irradiation-induced IL-6 release. After incubating PHGPx-overexpressing cells with PCOOHs a reduced induction of IL-6 was observed. This together with the suppression of UVA irradiation-induced IL-6 release in the presence of Trolox, a chain breaker of PCOOH-initiated lipid peroxidation, indicates that UVA irradiation-induced PCOOHs and subsequent lipid peroxides initiate the NFκB-mediated induction of IL-6, which mediates the induction of MMP-1. Our finding is particularly relevant in light of the already available small molecule mimetics of PHGPx.

Platinum-Based Compounds Induce Expression of p73 and Restores Drug- Sensitivity in p53 Dysfunctional Chronic Lymphocytic Leukemia (CLL) Cells.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2102-2102
Author(s):  
Sanne H. Tonino ◽  
Chantal Mulkens ◽  
Yoshinori Nonomura ◽  
Guangli Suo ◽  
Thomas J. Kipps ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Target Genes ◽  
Nuclear Translocation ◽  
De Novo ◽  
The United States ◽  
Lymphocytic Leukemia ◽  
Induced Expression ◽  
Platinum Based Chemotherapy ◽  
Fludarabine Monophosphate ◽  
Dependent Pathway

Abstract Chronic lymphocytic leukemia (CLL) cells can lose function of P53 and acquire resistance to standard chemotherapy. We found that expression P73, a member of the P53 family, could be induced in CLL cells following CD40-ligation via a c-abl dependent pathway. Induced expression of P73 was associated with re-acquired sensitivity to drugs commonly used treat this disease, such as Fludarabine monophosphate. Similar effects also were noted for CLL cells transduced with an adenovirus vector encoding P731. Prior studies found that P73 also can be induced in breast and colon cancer cell lines following treatment with platinum-based compounds, potentially accounting for the activity of this class of drugs. We hypothesized that treatment of CLL cells with such compound also could induce P73 and that such induced expression also might be associated with re-acquired sensitivity of P53-deficient CLL cells to standard anti-cancer drugs. We studied the mechanisms and effects of platinum-based compounds on CLL cells lacking functional p53. Studies were done with both the p3 dysfunctional pro-lymphocytic celline MEC-1 and with primary CLL cells that lacked functional P53. Treatment of MEC-1 cells with cisplatinum or oxaliplatin induced nuclear translocation of c-Abl in several hours, which was subsequently followed by expression of P73, and then its putative target genes, encoding Bid, p21 and Fas (CD95). Platinum-induced expression of these P73-target genes could be inhibited by co-treatment of the cells with the c-Abl inhibitor imatinib. Cisplatinum treatment of MEC-1 cells resulted in cell cycle arrest. Furthermore, cis-platinum treatment of MEC-1 cells or P53-deficient CLL cells synergized with Fas-mediated apoptosis, and importantly resulted in acquired sensitivity to the drug fludarabine monophosphate in vitro, apparently via a c-Abl dependent pathway. Purified p53 dysfunctional CLL cells obtained before and after 24 and 48 hrs of in vivo cisplatinum treatment revealed de novo expression of both P73 and Bid, illustrating induction of P73 at therapeutic dosages of cisplatin. This study indicates that platinum treatment of CLL cells induces c-Abl dependent expression of P73, which can enhance the sensitivity of P53-deficient CLL cells to drugs such as fludarabine monophosphate. These results provide additional incentive to investigate the activity of platinum-based chemotherapy regimens in patients with refractory disease who have CLL cells lacking functional P53, which currently are ongoing in Europe and the United States.

scholarly journals Suppression of Proinflammatory Cytokines and Mediators in LPS-Induced RAW 264.7 Macrophages by Stem Extract of Alternanthera sessilis via the Inhibition of the NF-κB Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Katyakyini Muniandy ◽  
Sivapragasam Gothai ◽  
Khaleel M. H. Badran ◽  
S. Suresh Kumar ◽  
Norhaizan Mohd Esa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Proinflammatory Cytokines ◽  
Nuclear Translocation ◽  
Raw 264.7 ◽  
Alternanthera Sessilis ◽  
B Subunit ◽  
Proinflammatory Mediators ◽  
Short Period ◽  
Stem Extract ◽  
Cox 2

Alternanthera sessilis, an edible succulent herb, has been widely used as herbal drug in many regions around the globe. Inflammation is a natural process of the innate immune system, accompanied with the increase in the level of proinflammatory mediators, for example, nitric oxide (NO) and prostaglandin (PGE2); cytokines such as interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNFα); and enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) via the activation and nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit p65 due to the phosphorylation of inhibitory protein, IκBα. Inflammation over a short period of time is essential for its therapeutic effect. However, prolonged inflammation can be detrimental as it is related to many chronic diseases such as delayed wound healing, cardiovascular disease, arthritis, and autoimmune disorders. Therefore, ways to curb chronic inflammation have been extensively investigated. In line with that, in this present study, we attempted to study the suppression activity of the proinflammatory cytokines and mediators as a characteristic of anti-inflammatory action, by using stem extract of A. sessilis in the lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophage cell line. The results showed that the extract has significantly inhibited the production of the proinflammatory mediators including NO and PGE2; cytokines comprising IL-6, IL-1β, and TNFα; and enzymes covering the iNOS and COX-2 by preventing the IκBα from being degraded, to inhibit the nuclear translocation of NF-κB subunit p65 in order to hinder the inflammatory pathway activation. These results indicated that the stem extract of A. sessilis could be an effective candidate for ameliorating inflammatory-associated complications.

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