scholarly journals BAY 11-7082 Is a Broad-Spectrum Inhibitor with Anti-Inflammatory Activity against Multiple Targets

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jaehwi Lee ◽  
Man Hee Rhee ◽  
Eunji Kim ◽  
Jae Youl Cho
Keyword(s):  
Inflammatory Responses ◽  
Janus Kinase ◽  
Prostaglandin E ◽  
Activator Protein 1 ◽  
Toll Like Receptor 4 ◽  
Multiple Targets ◽  
Extracellular Signal ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Necrosis Factor

BAY 11-7082 (BAY) is an inhibitor ofκB kinase (IKK) that has pharmacological activities that include anticancer, neuroprotective, and anti-inflammatory effects. In this study, BAY-pharmacological target pathways were further characterized to determine how this compound simultaneously suppresses various responses. Primary and cancerous (RAW264.7 cells) macrophages were activated by lipopolysaccharide, a ligand of toll-like receptor 4. As reported previously, BAY strongly suppressed the production of nitric oxide, prostaglandin E2, and tumor necrosis factor-αand reduced the translocation of p65, major subunit of nuclear factor-κB, and its upstream signaling events such as phosphorylation of IκBα, IKK, and Akt. In addition, BAY also suppressed the translocation and activation of activator protein-1, interferon regulatory factor-3, and signal transducer and activator of transcription-1 by inhibiting the phosphorylation or activation of extracellular signal-related kinase, p38, TANK-binding protein, and Janus kinase-2. These data strongly suggest that BAY is an inhibitor with multiple targets and could serve as a lead compound in developing strong anti-inflammatory drugs with multiple targets in inflammatory responses.

scholarly journals Myrrh Inhibits LPS-Induced Inflammatory Response and Protects from Cecal Ligation and Puncture-Induced Sepsis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Min-Sun Kim ◽  
Gi-Sang Bae ◽  
Kyoung-Chel Park ◽  
Bon Soon Koo ◽  
Byung-Jin Kim ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Inflammatory Responses ◽  
Cecal Ligation ◽  
Inhibitory Effect ◽  
Peritoneal Macrophages ◽  
Prostaglandin E ◽  
Cecal Ligation And Puncture ◽  
Extracellular Signal ◽  
Alanine Aminotransferase Level ◽  
Anti Inflammatory

Myrrh has been used as an antibacterial and anti-inflammatory agent. However, effect of myrrh on peritoneal macrophages and clinically relevant models of septic shock, such as cecal ligation and puncture (CLP), is not well understood. Here, we investigated the inhibitory effect and mechanism(s) of myrrh on inflammatory responses. Myrrh inhibited LPS-induced productions of inflammatory mediators such as nitric oxide, prostaglandin E2, and tumor necrosis factor-αbut not of interleukin (IL)-1βand IL-6 in peritoneal macrophages. In addition, Myrrh inhibited LPS-induced activation of c-jun NH2-terminal kinase (JNK) but not of extracellular signal-regulated kinase (ERK), p38, and nuclear factor-κB. Administration of Myrrh reduced the CLP-induced mortality and bacterial counts and inhibited inflammatory mediators. Furthermore, administration of Myrrh attenuated CLP-induced liver damages, which were mainly evidenced by decreased infiltration of leukocytes and aspartate aminotransferase/alanine aminotransferase level. Taken together, these results provide the evidence for the anti-inflammatory and antibacterial potential of Myrrh in sepsis.

scholarly journals Beyond the guidelines management of juvenile idiopathic arthritis: a case report of a girl with polyarticular disease refractory to multiple treatment options and Leri Weill syndrome

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Vana Vukić ◽  
Ana Smajo ◽  
Mandica Vidović ◽  
Rudolf Vukojević ◽  
Miroslav Harjaček ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Case Report ◽  
Treatment Options ◽  
Janus Kinase ◽  
Musculoskeletal Symptoms ◽  
Multiple Treatment ◽  
Number Of Patients ◽  
Systemic Glucocorticoids ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Abstract Background The last two decades brought new treatment options and high quality guidelines into the paediatric rheumatologic practice. Nevertheless, a number of patients still present a diagnostic and therapeutic challenge due to combination of vague symptoms and unresponsiveness to available treatment modalities. Case presentation We report a case of sixteen years old girl suffering from polyarticular type of juvenile idiopathic arthritis refractory to multiple treatment options. She first presented at the age of 4 with swelling and contractures of both knees. Her symptoms were initially unresponsive to nonsteroidal anti-inflammatory drugs and progressed despite treatment with intraarticular and systemic glucocorticoids and methotrexate. Throughout the years, she received several biologics together with continuous administration of nonsteroidal anti-inflammatory drugs and disease modifying anti-rheumatic drugs as well as intraarticular and systemic glucocorticoids in disease flares. However, none of this options  provided a permanent remission, so various other modalities, as well as other possible diagnoses were constantly being considered. Eventually she became dependent on a daily dose of systemic glucocorticoids. In 2018, the treatment with Janus kinase inhibitor tofacitinib was initiated, which led to gradual amelioration of musculoskeletal symptoms, improvement of inflammatory markers and overall well-being, as well as to the weaning of systemic glucocorticoids. As the swelling of the wrists subsided for the first time in many years, Madelung’s deformity was noticed, first clinically, and later radiographically as well. Genetic analysis revealed short-stature homeobox gene deficiency and confirmed the diagnosis of Leri Weill syndrome. Conclusions This case report emphasizes the need for reporting refractory, complicated cases from everyday clinical practice in order to build-up the overall knowledge and share experience which is complementary to available guidelines. Individual reports of difficult to treat cases, especially when additional diagnoses are involved, can be helpful for physicians treating patients with common rheumatological diseases such as juvenile idiopathic arthritis.

scholarly journals Preventive Effects of a Kampo Medicine, Kakkonto, on Inflammatory Responses via the Suppression of Extracellular Signal-Regulated Kinase Phosphorylation in Lipopolysaccharide-Treated Human Gingival Fibroblasts

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hiroyuki Kitamura ◽  
Hiroko Urano ◽  
Toshiaki Ara
Keyword(s):  
Periodontal Disease ◽  
Inflammatory Responses ◽  
Human Gingival Fibroblasts ◽  
Kampo Medicine ◽  
Prostaglandin E ◽  
Gingival Fibroblasts ◽  
Extracellular Signal Regulated Kinase ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
Cox 2

Periodontal disease is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss in severe clinical cases. The chemical mediator prostaglandin E2 (PGE2) and cytokines such as interleukin- (IL-)6 and IL-8 have been known to play important roles in inflammatory responses and tissue degradation. In the present study, we investigated the effects of a kampo medicine, kakkonto (TJ-1), on the production of prostaglandin E2 (PGE2), IL-6, and IL-8 by human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) from Porphyromonas gingivalis. Kakkonto concentration dependently suppressed LPS-induced PGE2 production but did not alter basal PGE2 levels. In contrast, kakkonto significantly increased LPS-induced IL-6 and IL-8 production. Kakkonto decreased cyclooxygenase- (COX-)1 activity to approximately 70% at 1 mg/mL but did not affect COX-2 activity. Kakkonto did not affect cytoplasmic phospholipase A2 (cPLA2), annexin1, or LPS-induced COX-2 expression. Kakkonto suppressed LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation, which is known to lead to ERK activation and cPLA2 phosphorylation. These results suggest that kakkonto decreased PGE2 production by inhibition of ERK phosphorylation which leads to inhibition of cPLA2 phosphorylation and its activation. Therefore, kakkonto may be useful to improve gingival inflammation in periodontal disease.

scholarly journals Activated Platelets Induce an Anti-Inflammatory Response of Monocytes/Macrophages through Cross-Regulation of PGE2and Cytokines

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Bona Linke ◽  
Yannick Schreiber ◽  
Bettina Picard-Willems ◽  
Patrick Slattery ◽  
Rolf M. Nüsing ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Innate Immune ◽  
Prostaglandin E ◽  
Murine Bone Marrow ◽  
Activated Platelets ◽  
Monocytes And Macrophages ◽  
Inflammatory Processes ◽  
Necrosis Factor

Platelets are well known for their role in hemostasis and are also increasingly recognized for their roles in the innate immune system during inflammation and their regulation of macrophage activation. Here, we aimed to study the influence of platelets on the production of inflammatory mediators by monocytes and macrophages. Analyzing cocultures of platelets and murine bone marrow-derived macrophages or human monocytes, we found that collagen-activated platelets release high amounts of prostaglandin E2(PGE2) that leads to an increased interleukin- (IL-) 10 release and a decreased tumor necrosis factor (TNF)αsecretion out of the monocytes or macrophages. Platelet PGE2mediated the upregulation of IL-10 in both cell types via the PGE2receptor EP2. Notably, PGE2-mediated IL-10 synthesis was also mediated by EP4 in murine macrophages. Inhibition of TNFαsynthesis via EP2 and EP4, but not EP1, was mediated by IL-10, since blockade of the IL-10 receptor abolished the inhibitory effect of both receptors on TNFαrelease. This platelet-mediated cross-regulation between PGE2and cytokines reveals one mechanism how monocytes and macrophages can attenuate excessive inflammatory responses induced by activated platelets in order to limit inflammatory processes.

scholarly journals Phytosterols Suppress Phagocytosis and Inhibit Inflammatory Mediators via ERK Pathway on LPS-Triggered Inflammatory Responses in RAW264.7 Macrophages and the Correlation with Their Structure

Foods ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 582 ◽  
Author(s):  
Yuan ◽  
Zhang ◽  
Shen ◽  
Jia ◽  
Xie
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Responses ◽  
Ester Group ◽  
No Production ◽  
Raw264.7 Macrophages ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase

Phytosterols, found in many commonly consumed foods, exhibit a broad range of physiological activities including anti-inflammatory effects. In this study, the anti-inflammatory effects of ergosterol, β-sitosterol, stigmasterol, campesterol, and ergosterol acetate were investigated in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Results showed that all phytosterol compounds alleviated the inflammatory reaction in LPS-induced macrophage models; cell phagocytosis, nitric oxide (NO) production, release of tumor necrosis factor-α (TNF-α), and expression and activity of pro-inflammatory mediator cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and phosphorylated extracellular signal-regulated protein kinase (p-ERK) were all inhibited. The anti-inflammatory activity of β-sitosterol was higher than stigmasterol and campesterol, which suggests that phytosterols without a double bond on C-22 and with ethyl on C-24 were more effective. However, inconsistent results were observed upon comparison of ergosterol and ergosterol acetate (hydroxy or ester group on C-3), which suggest that additional research is still needed to ascertain the contribution of structure to their anti-inflammatory effects.

scholarly journals Effect of Kramecyne on the Inflammatory Response in Lipopolysaccharide-Stimulated Peritoneal Macrophages

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
E. Sánchez-Miranda ◽  
J. Lemus-Bautista ◽  
S. Pérez ◽  
J. Pérez-Ramos
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Peritoneal Macrophages ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
North And South America ◽  
North And South ◽  
Mouse Peritoneal Macrophages ◽  
Necrosis Factor

Kramecyne is a new peroxide, it was isolated fromKrameria cytisoides, methanol extract, and this plant was mostly found in North and South America. This compound showed potent anti-inflammatory activity; however, the mechanisms by which this compound exerts its anti-inflammatory effect are not well understood. In this study, we examined the effects of kramecyne on inflammatory responses in mouse lipopolysaccharide- (LPS-) induced peritoneal macrophages. Our findings indicate that kramecyne inhibits LPS-induced production of tumor necrosis factor (TNF-α) and interleukin- (IL-) 6. During the inflammatory process, levels of cyclooxygenase- (COX-) 2, nitric oxide synthase (iNOS), and nitric oxide (NO) increased in mouse peritoneal macrophages; however, kramecyne suppressed them significantly. These results provide novel insights into the anti-inflammatory actions and support its potential use in the treatment of inflammatory diseases.

scholarly journals Challenges and Opportunities from Targeting Inflammatory Responses to SARS-CoV-2 Infection: A Narrative Review

2020 ◽  
Vol 9 (12) ◽  
pp. 4021
Author(s):  
Vincenzo Lariccia ◽  
Simona Magi ◽  
Tiziano Serfilippi ◽  
Marwa Toujani ◽  
Santo Gratteri ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Early Stage ◽  
Clinical Care ◽  
Current Evidence ◽  
Global Pandemic ◽  
Challenges And Opportunities ◽  
Inflammatory Processes ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Novel Coronavirus

The novel coronavirus disease 2019 (COVID-19) is a global pandemic that continues to sweep across the world, posing an urgent need for effective therapies and prevention of the spread of the severe acute respiratory syndrome related to coronavirus-2 (SARS-CoV-2). A major hypothesis that is currently guiding research and clinical care posits that an excessive and uncontrolled surge of pro-inflammatory cytokines (the so-called “cytokine storm”) drives morbidity and mortality in the most severe cases. In the overall efforts made to develop effective and safe therapies (including vaccines) for COVID-19, clinicians are thus repurposing ready-to-use drugs with direct or indirect anti-inflammatory and immunomodulatory activities. Speculatively, there are many opportunities and challenges in targeting immune/inflammatory processes in the evolving settings of COVID-19 disease because of the need to safely balance the fight against virus and aggressive inflammation versus the suppression of host immune defenses and the risk of additional harms in already compromised patients. To this end, many studies are globally underway to weigh the pros and cons of tailoring drugs used for inflammatory-driven conditions to COVID-19 patient care, and the next step will be to summarize the growing clinical trial experience into clean clinical practice. Based on the current evidence, anti-inflammatory drugs should be considered as complementary approaches to anti-viral drugs that need to be timely introduced in the management of COVID-19 according to disease severity. While drugs that target SARS-CoV-2 entry or replication are expected to confer the greatest benefits at the early stage of the infection, anti-inflammatory drugs would be more effective in limiting the inflammatory processes that drive the worsening of the disease.

scholarly journals Inhibition of Inflammatory Responses by Centella asiatica via Suppression of IRAK1-TAK1 in Mouse Macrophages

2020 ◽  
Vol 48 (05) ◽  
pp. 1103-1120
Author(s):  
Young-Chang Cho ◽  
Huong Lan Vuong ◽  
Jain Ha ◽  
Sewoong Lee ◽  
Jiyoung Park ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Centella Asiatica ◽  
Prostaglandin E ◽  
Methanol Fraction ◽  
Raw 264.7 Macrophages ◽  
Inflammatory Mechanism ◽  
Mouse Macrophages ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Centella asiatica (L.) Urb. (C. asiatica) has been widely treated for inflammation-related diseases in China for thousands of years. While C. asiatica showed relevant effects as traditional medicine, the mechanism of C. asiatica suppressing inflammation has not been thoroughly investigated. Therefore, this study was conducted to reveal the anti-inflammatory mechanism of methanol fraction from C. asiatica (MCA) at the molecular level in murine macrophages. Levels of inflammation-related mediators were observed with treatment of MCA. MCA significantly suppressed nitric oxide production and iNOS expression in RAW 264.7 macrophages. Prostaglandin E2 production was alleviated by MCA via the downregulation of cyclooxygenase-2. MCA treatment also reduced pro-inflammatory tumor necrosis factor-[Formula: see text] and interleukin (IL)-6 levels. LPS/D-GalN-induced acute hepatitis in mouse was alleviated by MCA treatment. In addition, MCA decreased the phosphorylation of inhibitory [Formula: see text]B[Formula: see text] (I[Formula: see text]B[Formula: see text]) at Ser32/36 and thereby blocked I[Formula: see text]B[Formula: see text] degradation. TXY motif phosphorylation in the activation loops of mitogen-activated protein kinases (MAPKs) was also suppressed by MCA treatment. Further investigation revealed that MCA inhibited transforming growth factor-[Formula: see text]-activated kinase 1 (TAK1) phosphorylation and IL-1 receptor-associated kinase (IRAK1) degradation, the upstream kinases activating nuclear factor [Formula: see text]B and MAPKs. Taken together, MCA exhibited anti-inflammatory properties via the downregulation of IRAK1-TAK1 signaling pathways.

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