scholarly journals Inhibition of osteoclastogenesis and inflammation by phosvitin and phosvitin hydrolysate via NF-κB and MAPK pathways in RAW 264.7 cells

2021 ◽  
Vol 13 ◽  
Author(s):  
Jiandong Ren ◽  
Subhadeep Chakrabarti ◽  
Jianping Wu
Keyword(s):  
Raw264.7 Cells ◽  
Raw 264.7 Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tnf Α ◽  
Factor Alpha ◽  
Oxide Synthase

Phosvitin (PV) is an egg protein. Our recent study showed both phosvitin and phosvitin hydrolysate (PVH) could promote osteoblast differentiation in osteoblast cells. The objective of the study was to investigate the effects of PV and PVH on osteoclastogenesis and possible signalling pathways in RAW264.7 cells. Both PV and PVH inhibited osteoclastogenesis (fewer tartrate-resistant acid phosphatase (TRAP) positive cells and lower TRAP activity), reduced levels of transcription factors, c-Fos and NFATc1 (nuclear factor of activated T-cells, cytoplasmic 1), and suppressed inflammatory biomarkers TNF-α (tumor necrosis factor alpha), MCP-1 (monocyte chemoattractant protein 1), RANTES (regulated on activation, normal T cell expressed and secreted), and inducible nitric oxide synthase. The inhibitory effects of PV and PVH on RAW264.7 cells differentiation were likely mediated through p38, c-Jun N-terminal kinases (JNK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. These results indicated that PV and PVH might inhibit bone resorption activities.  

scholarly journals Anti-Neuroinflammatory and Anti-Inflammatory Activities of Phenylheptatriyne Isolated from the Flowers of Coreopsis lanceolata L. via NF-κB Inhibition and HO-1 Expression in BV2 and RAW264.7 Cells

2021 ◽  
Vol 22 (14) ◽  
pp. 7482
Author(s):  
Hwan Lee ◽  
Zhiming Liu ◽  
Chi-Su Yoon ◽  
Linsha Dong ◽  
Wonmin Ko ◽  
...  
Keyword(s):  
Silica Gel ◽  
Column Chromatography ◽  
Raw264.7 Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Etoac Fraction ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
And Oxidative Stress ◽  
Necrosis Factor

Aging is associated with immune disregulation and oxidative stress which lead to inflammation and neurodegenerative diseases. We have tried to identify the anti-neuroinflammatory and anti-inflammatory components of Coreopsis lanceolata L. The dried flowers of C. lanceolata were extracted with 70% EtOH, and the obtained extract was divided into CH2Cl2, EtOAc, n-BuOH, and H2O fractions. The CH2Cl2 fraction was separated using silica gel and C-18 column chromatography to yield phenylheptatriyne (1), 2′-hydroxy-3,4,4′-trimethoxychalcone (2), and 4′,7-dimethoxyflavanone (3). Additionally, the EtOAc fraction was subjected to silica gel, C-18, and Sephadex LH-20 column chromatography to yield 8-methoxybutin (4) and leptosidin (5). All the compounds isolated from C. lanceolata inhibited the production of nitric oxide (NO) in LPS-induced BV2 and RAW264.7 cells. In addition, phenylheptatriyne and 4′,7-dimethoxyflavanone reduced the secretion of inflammatory cytokines, tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6. Among them, phenylheptatriyne was significantly downregulated in the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequently, phenylheptatriyne also effectively inhibited nuclear factor-kappa B (NF-κB) activation in LPS-stimulated BV2 and RAW264.7 cells. Based on these results, the anti-neuroinflammatory effect of phenylheptatriyne isolated from C. lanceolata was confirmed, which may exert a therapeutic effect in treatment of neuroinflammation-related diseases.

scholarly journals Inhibition of Osteoclastogenesis by Thioredoxin-Interacting Protein-Derived Peptide (TN13)

2019 ◽  
Vol 8 (4) ◽  
pp. 431 ◽  
Author(s):  
Mi Kim ◽  
Won Kim ◽  
Jae-Eun Byun ◽  
Jung Choi ◽  
Suk Yoon ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Raw 264.7 Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Interacting Protein ◽  
Hematopoietic Stem ◽  
Thioredoxin Interacting Protein

Overactivated osteoclasts lead to many bone diseases, including osteoporosis and rheumatoid arthritis. The p38 MAPK (p38) is an essential regulator of the receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis and bone loss. We previously reported TAT conjugated thioredoxin-interacting protein-derived peptide (TAT-TN13) as an inhibitor of p38 in hematopoietic stem cells (HSCs). Here, we examined the role of TAT-TN13 in the differentiation and function of osteoclasts. TAT-TN13 significantly suppressed RANKL-mediated differentiation of RAW 264.7 cells and bone marrow macrophages (BMMs) into osteoclasts. TAT-TN13 also inhibited the RANKL-induced activation of NF-κB and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), leading to the decreased expression of osteoclast-specific genes, including tartrate-resistant acid phosphatase (TRAP) and Cathepsin K. Additionally, TAT-TN13 treatment protected bone loss in ovariectomized (OVX) mice. Taken together, these results suggest that TAT-TN13 inhibits osteoclast differentiation by regulating the p38 and NF-κB signaling pathway; thus, it may be a useful agent for preventing or treating osteoporosis.

scholarly journals Enzyme Degradation and Proinflammatory Activity in Arthritogenic and Nonarthritogenic Eubacterium aerofaciens Cell Walls

2001 ◽  
Vol 69 (12) ◽  
pp. 7277-7284 ◽  
Author(s):  
Xiang Zhang ◽  
Marja Rimpiläinen ◽  
Egle Šimelyte ◽  
Paavo Toivanen
Keyword(s):  
Proinflammatory Cytokines ◽  
Chronic Arthritis ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Enzyme Degradation ◽  
Tnf Α ◽  
Stimulatory Capacity ◽  
Normal Human ◽  
Proinflammatory Activity ◽  
Factor Alpha

ABSTRACT Two almost-identical strains of Eubacterium aerofaciens isolated from the normal human gut flora were used. The cell wall (CW) of one strain with a peptidoglycan (PG) type A4α induces chronic arthritis in the rat after a single intraperitoneal injection, whereas CW of the other with PG type A4β induces only a transient acute arthritis. The CW of the arthritogenic E. aerofaciens was a twofold-more-potent stimulator of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) than the nonarthritogenic CW. After degradation with mutanolysin, the capacity of the arthritogenic PG to stimulate production of TNF-α and MCP-1 was significantly increased, whereas that of the nonarthritogenic PG was significantly decreased. In other words, after enzyme degradation the arthritogenic PG had a four- to fivefold-stronger stimulatory capacity than that of the enzyme-treated nonarthritogenic PG. These findings indicate that the arthritogenicity of CW or a PG is not dependent on the enzyme resistance alone but also on how the PG fragments released by enzyme degradation stimulate the production of proinflammatory cytokines.

scholarly journals Immunogenicity and Protection Induced by a Mycobacterium tuberculosissigE Mutant in a BALB/c Mouse Model of Progressive Pulmonary Tuberculosis

2010 ◽  
Vol 78 (7) ◽  
pp. 3168-3176 ◽  
Author(s):  
Rogelio Hernandez Pando ◽  
Leon Diana Aguilar ◽  
Issar Smith ◽  
Riccardo Manganelli
Keyword(s):  
Mutant Strain ◽  
Virulent Strain ◽  
Survival Rates ◽  
Live Vaccine ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Oxide Synthase ◽  
Necrosis Factor ◽  
Inducible Nitric Oxide

ABSTRACT Tuberculosis is still one of the main challenges to human global health, leading to about two million deaths every year. One of the reasons for its success is the lack of efficacy of the widely used vaccine Mycobacterium bovis BCG. In this article, we analyze the potential use of an attenuated mutant of Mycobacterium tuberculosis H37Rv lacking the sigma factor σE as a live vaccine. We have demonstrated that BALB/c mice infected by the intratracheal route with this mutant strain showed significantly higher survival rates and less tissue damage than animals infected with the parental or complemented mutant strain. Although animals infected with the sigE mutant had low bacillary loads, their lungs showed significantly higher production of the protective factors gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS), and β-defensins than those of animals infected with the parental or complemented mutant strain. Moreover, we demonstrate that the sigE mutant, when inoculated subcutaneously, was more attenuated than BCG in immunodeficient nude mice, thus representing a good candidate for a novel attenuated live vaccine strain. Finally, when we used the sigE mutant as a subcutaneous vaccine, it was able to induce a higher level of protection than did BCG with both H37Rv and a highly virulent strain of M. tuberculosis (Beijing code 9501000). Taken together, our findings suggest that the sigE mutant is a very promising strain for the development of a new vaccine against tuberculosis.

scholarly journals Involvement of Inflammatory Chemokines in Survival of Human Monocytes Fed with Malarial Pigment

2010 ◽  
Vol 78 (11) ◽  
pp. 4912-4921 ◽  
Author(s):  
Giuliana Giribaldi ◽  
Mauro Prato ◽  
Daniela Ulliers ◽  
Valentina Gallo ◽  
Evelin Schwarzer ◽  
...  
Keyword(s):  
Real Time ◽  
Expression Patterns ◽  
Human Monocytes ◽  
Rt Pcr ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Inflammatory Protein ◽  
Tnf Α ◽  
Inflammatory Chemokines ◽  
Factor Alpha

ABSTRACT Hemozoin (HZ)-fed monocytes are exposed to strong oxidative stress, releasing large amounts of peroxidation derivatives with subsequent impairment of numerous functions and overproduction of proinflammatory cytokines. However, the histopathology at autopsy of tissues from patients with severe malaria showed abundant HZ in Kupffer cells and other tissue macrophages, suggesting that functional impairment and cytokine production are not accompanied by cell death. The aim of the present study was to clarify the role of HZ in cell survival, focusing on the qualitative and temporal expression patterns of proinflammatory and antiapoptotic molecules. Immunocytochemical and flow cytometric analyses showed that the long-term viability of human monocytes was unaffected by HZ. Short-term analysis by macroarray of a complete panel of cytokines and real-time reverse transcription (RT)-PCR experiments showed that HZ immediately induced interleukin-1β (IL-1β) gene expression, followed by transcription of eight additional chemokines (IL-8, epithelial cell-derived neutrophil-activating peptide 78 [ENA-78], growth-regulated oncogene α [GROα], GROβ, GROγ, macrophage inflammatory protein 1α [MIP-1α], MIP-1β, and monocyte chemoattractant protein 1 [MCP-1]), two cytokines (tumor necrosis factor alpha [TNF-α] and IL-1receptor antagonist [IL-1RA]), and the cytokine/chemokine-related proteolytic enzyme matrix metalloproteinase 9 (MMP-9). Furthermore, real-time RT-PCR showed that 15-HETE, a potent lipoperoxidation derivative generated by HZ through heme catalysis, recapitulated the effects of HZ on the expression of four of the chemokines. Intermediate-term investigation by Western blotting showed that HZ increased expression of HSP27, a chemokine-related protein with antiapoptotic properties. Taken together, the present data suggest that apoptosis of HZ-fed monocytes is prevented through a cascade involving 15-HETE-mediated upregulation of IL-1β transcription, rapidly sustained by chemokine, TNF-α, MMP-9, and IL-1RA transcription and upregulation of HSP27 protein expression.

Nuclear Factor κB and Anesthetic Preconditioning during Myocardial Ischemia-Reperfusion

2004 ◽  
Vol 100 (3) ◽  
pp. 540-546 ◽  
Author(s):  
Caiyun Zhong ◽  
Yamei Zhou ◽  
Hong Liu
Keyword(s):  
Ischemia Reperfusion ◽  
Interleukin 1 ◽  
Intercellular Adhesion Molecule ◽  
Nuclear Factor ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Nf Kappab ◽  
Myocardial Ischemia Reperfusion ◽  
Oxide Synthase

Background Volatile anesthetic preconditioning (APC) protects against myocardial ischemia-reperfusion (IR) injury, but the precise mechanisms underlying this phenomenon remain undefined. To investigate the molecular mechanism of APC in myocardial protection, the activation of nuclear factor (NF) kappaB and its regulated inflammatory mediators expression were examined in the current study. Methods Hearts from male rats were isolated, Langendorff perfused, and randomly assigned to one of three groups: (1) the control group: hearts were continuously perfused for 130 min; (2) the IR group: 30 min of equilibration, 15 min of baseline, 25 min of ischemia, 60 min of reperfusion; and (3) the APC + IR group: 30 min of equilibration, 10 min of sevoflurane exposure and a 5-min washout, 25 min of global ischemia, 60 min of reperfusion. Tissue samples were acquired at the end of reperfusion. NF-kappaB activity was determined by electrophoretic mobility shift assay. The NF-kappaB inhibitor, IkappaB-alpha, was determined by Western blot analysis. Myocardial inflammatory mediators, including tumor necrosis factor alpha, interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase, were also assessed by Western blot analysis. Results Nuclear factor kappaB-DNA binding activity was significantly increased at the end of reperfusion in rat myocardium, and cytosolic IkappaB-alpha was decreased. Supershift assay revealed the involvement of NF-kappaB p65 and p50 subunits. APC with sevoflurane attenuated NF-kappaB activation and reduced the expression of tumor necrosis factor alpha, interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase. APC also reduced infarct size and creatine kinase release and improved myocardial left ventricular developed pressure during IR. Conclusions The results of this study indicate that attenuation of NF-kappaB activation and subsequent down-regulation of NF-kappaB-dependent inflammatory gene expression plays an important role in the protective mechanism of APC against acute myocardial IR injury.

Triterpenoid CDDO-IM protects against lipopolysaccharide-induced inflammatory response and cytotoxicity in macrophages: The involvement of the NF-κB signaling pathway

2022 ◽  
pp. 153537022110669
Author(s):  
Hassan Ahmed ◽  
Urooj Amin ◽  
Xiaolun Sun ◽  
Demetrius R Pitts ◽  
Yunbo Li ◽  
...  
Keyword(s):  
Septic Shock ◽  
Inflammatory Cytokine ◽  
Interleukin 1 ◽  
Severe Form ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Factor Alpha ◽  
Gene Expression Levels

Lipopolysaccharide (LPS), also known as endotoxin, can trigger septic shock, a severe form of inflammation-mediated sepsis with a very high mortality rate. However, the precise mechanisms underlying this endotoxin remain to be defined and detoxification of LPS is yet to be established. Macrophages, a type of immune cells, initiate a key response responsible for the cascade of events leading to the surge in inflammatory cytokines and immunopathology of septic shock. This study was undertaken to determine whether the LPS-induced inflammation in macrophage cells could be ameliorated via CDDO-IM (2-cyano-3,12 dioxooleana-1,9 dien-28-oyl imidazoline), a novel triterpenoid compound. Data from this study show that gene expression levels of inflammatory cytokine genes such as interleukin-1 beta (IL-1β), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) were considerably increased by treatment with LPS in macrophages differentiated from ML-1 monocytes. Interestingly, LPS-induced increase in expression of pro-inflammatory cytokine levels is reduced by CDDO-IM. In addition, endogenous upregulation of a series of antioxidant molecules by CDDO-IM provided protection against LPS-induced cytotoxicity in macrophages. LPS-mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) transcriptional activity was also noted to decrease upon treatment with CDDO-IM in macrophages suggesting the involvement of the NF-κB signaling. This study would contribute to improve our understanding of the detoxification of endotoxin LPS by the triterpenoid CDDO-IM.

scholarly journals A Novel, Tumor-Induced Osteoclastogenesis Pathway Insensitive to Denosumab but Interfered by Cannabidiol

2019 ◽  
Vol 20 (24) ◽  
pp. 6211
Author(s):  
Maiko Tsuchiya ◽  
Kou Kayamori ◽  
Akane Wada ◽  
Motohiro Komaki ◽  
Yae Ohata ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Metabolism ◽  
Nuclear Factor ◽  
Necrosis Factor Alpha ◽  
Local Bone ◽  
Tnf Α ◽  
Psychotropic Effects ◽  
Factor Alpha ◽  
Culture Supernatants ◽  
Necrosis Factor

Bone metabolism is strictly regulated, and impaired regulation caused by hormonal imbalances induces systemic bone loss. Local bone loss caused by tumor invasion into bone is suggested to be induced by the generation of cytokines, which affect bone metabolism, by tumor cells. The major cause of systemic and local bone losses is excess bone resorption by osteoclasts, which differentiate from macrophages by receptor activator of nuclear factor kappa-B ligand (RANKL) or tumor necrosis factor-alpha (TNF-α). We previously found a novel pathway for tumor-induced osteoclastogenesis targeting osteoclast precursor cells (OPCs). Tumor-induced osteoclastogenesis was resistant to RANKL and TNF-α inhibitors. In the present study, we confirmed that exosomes derived from oral squamous cell carcinoma (OSCC) cells induced osteoclasts from OPCs. We also showed that the depletion of exosomes from culture supernatants of OSCC cells partially interfered with osteoclastogenesis, and cannabidiol, an innoxious cannabinoid without psychotropic effects, almost completely suppressed tumor-induced osteoclastogenesis. Osteoclastogenesis and its interference by cannabidiol were independent of the expression of nuclear factor of T cell c1 (NFATc1). These results show that osteoclastogenesis induced by OSCC cells targeting OPCs is a novel osteoclastogenic pathway independent of NFATc1 expression that is partially caused by tumor-derived exosomes and suppressed by cannabidiol.

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