scholarly journals Isoleucilactucin Ameliorates Coal Fly Ash-Induced Inflammation through the NF-κB and MAPK Pathways in MH-S Cells

2021 ◽  
Vol 22 (17) ◽  
pp. 9506
Author(s):  
H. M. Arif Ullah ◽  
Tae-Hyung Kwon ◽  
SeonJu Park ◽  
Sung Dae Kim ◽  
Man Hee Rhee
Keyword(s):  
Fly Ash ◽  
Nuclear Translocation ◽  
Coal Fly Ash ◽  
Mitogen Activated Protein Kinase ◽  
Active Constituent ◽  
Mapk Pathways ◽  
Proinflammatory Mediators ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

We investigated whether isoleucilactucin, an active constituent of Ixeridium dentatum, reduces inflammation caused by coal fly ash (CFA) in alveolar macrophages (MH-S). The anti-inflammatory effects of isoleucilactucin were assessed by measuring the concentration of nitric oxide (NO) and the expression of pro-inflammatory mediators in MH-S cells exposed to CFA-induced inflammation. We found that isoleucilactucin reduced CFA-induced NO generation dose-dependently in MH-S cells. Moreover, isoleucilactucin suppressed CFA-activated proinflammatory mediators, including cyclooxygenase-2 (COX2) and inducible NO synthase (iNOS), and the proinflammatory cytokines such as interleukin-(IL)-1β, IL-6, and tumor necrosis factor (TNF-α). The inhibiting properties of isoleucilactucin on the nuclear translocation of phosphorylated nuclear factor-kappa B (p-NF-κB) were observed. The effects of isoleucilactucin on the NF-κB and mitogen-activated protein kinase (MAPK) pathways were also measured in CFA-stimulated MH-S cells. These results indicate that isoleucilactucin suppressed CFA-stimulated inflammation in MH-S cells by inhibiting the NF-κB and MAPK pathways, which suggest it might exert anti-inflammatory properties in the lung.

scholarly journals Anti-Inflammatory Effects of Moxifloxacin on Activated Human Monocytic Cells: Inhibition of NF-κB and Mitogen-Activated Protein Kinase Activation and of Synthesis of Proinflammatory Cytokines

2004 ◽  
Vol 48 (6) ◽  
pp. 1974-1982 ◽  
Author(s):  
Taly Weiss ◽  
Itamar Shalit ◽  
Hannah Blau ◽  
Sara Werber ◽  
Drora Halperin ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Nuclear Translocation ◽  
Human Peripheral Blood ◽  
Mitogen Activated Protein Kinase ◽  
Blood Monocytes ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory ◽  
Activated Monocytes

ABSTRACT We previously showed that moxifloxacin (MXF) exerts protective anti-inflammatory effects in immunosuppressed mice infected with Candida albicans by inhibiting interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α) production in the lung. Immunohistochemistry demonstrated inhibition of nuclear factor (NF)-κB translocation in lung epithelium and macrophages in MXF-treated mice. In the present study we investigated the effects of MXF on the production of proinflammatory cytokines (i.e., IL-8, TNF-α, and IL-1β) by activated human peripheral blood monocytes and THP-1 cells and analyzed the effects of the drug on the major signal transduction pathways associated with inflammation: NF-κB and the mitogen-activated protein kinases ERK and c-Jun N-terminal kinase (JNK). The levels of IL-8, TNF-α, and IL-1β secretion rose 20- and 6.7-fold in lipopolysaccharide (LPS)-activated monocytes and THP-1 cells, respectively. MXF (5 to 20 μg/ml) significantly inhibited cytokine production by 14 to 80% and 15 to 73% in monocytes and THP-1 cells, respectively. In THP-1 cells, the level of NF-κB nuclear translocation increased fourfold following stimulation with LPS-phorbol myristate acetate (PMA), and this was inhibited (38%) by 10 μg of MXF per ml. We then assayed the degradation of inhibitor (I)-κB by Western blotting. LPS-PMA induced degradation of I-κB by 73%, while addition of MXF (5 μg/ml) inhibited I-κB degradation by 49%. Activation of ERK1/2 and the 46-kDa p-JNK protein was enhanced by LPS and LPS-PMA and was significantly inhibited by MXF (54 and 42%, respectively, with MXF at 10 μg/ml). We conclude that MXF suppresses the secretion of proinflammatory cytokines in human monocytes and THP-1 cells and that it exerts its anti-inflammatory effects in THP-1 cells by inhibiting NF-κB, ERK, and JNK activation. Its anti-inflammatory properties should be further assessed in clinical settings.

scholarly journals Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway

2017 ◽  
Vol 43 (2) ◽  
pp. 540-552 ◽  
Author(s):  
Hany H. Arab ◽  
Samir A. Salama ◽  
Tamer M. Abdelghany ◽  
Hany A. Omar ◽  
El-Shaimaa A. Arafa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mapk Pathway ◽  
Lipid Peroxide ◽  
Mitogen Activated Protein Kinase ◽  
Camel Milk ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory

Background/Aims: Camel milk (CM) has shown beneficial anti-inflammatory actions in several experimental and clinical settings. So far, its effect on rheumatoid arthritis (RA) has not been previously explored. Thus, the current work aimed to evaluate the effects of CM in Adjuvant-induced arthritis and air pouch edema models in rats, which mimic human RA. Methods: CM was administered at 10 ml/kg orally for 3 weeks starting on the day of Freund’s adjuvant paw inoculation. The levels of TNF-α and IL-10 were measured by ELISA while the protein expression of NF-κBp65, COX-2 and iNOS was detected by immunohistochemistry. The expression of MAPK target proteins was assessed by Western blotting. Results: CM attenuated paw edema, arthritic index and gait score along with dorsal pouch inflammatory cell migration. CM lowered the TNF-α and augmented the anti-inflammatory IL-10 levels in sera and exudates of arthritic rats. It also attenuated the expression of activated NF-κBp65, COX-2 and iNOS in the lining of the dorsal pouch. Notably, CM inhibited the MAPK pathway signal transduction via lowering the phosphorylation of p38 MAPK, ERK1/2 and JNK1/2 in rat hind paws. Additionally, CM administration lowered the lipid peroxide and nitric oxide levels and boosted glutathione and total anti-oxidant capacity in sera and exudates of animals. Conclusion: The observed CM downregulation of the arthritic process may support the interest of CM consumption as an adjunct approach for the management of RA.

scholarly journals Duchesnea indica Extract Attenuates Coal Fly Ash-Induced Inflammation in Murine Alveolar Macrophages through the NF-Kappa B Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
H. M. Arif Ullah ◽  
Yuan Yee Lee ◽  
Sung Dae Kim ◽  
Man Hee Rhee
Keyword(s):  
Nitric Oxide ◽  
Fly Ash ◽  
Western Blotting ◽  
Alveolar Macrophages ◽  
Coal Fly Ash ◽  
Gas Chromatography Mass Spectrometry ◽  
No Production ◽  
Proinflammatory Mediators ◽  
Duchesnea Indica ◽  
Anti Inflammatory

Duchesnea indica is known as false strawberry, is found in East Asia, and has numerous biological properties. The aim of this study was to investigate the anti-inflammatory effect of Duchesnea indica extract (DIE) on coal fly ash- (CFA-) induced inflammation in murine alveolar macrophages (MH-S). Following the induction of inflammation in MH-S cells by CFA, nitric oxide (NO) was measured to evaluate the anti-inflammatory property of DIE. Cell viability and inflammatory gene expression were analyzed using polymerase chain reaction (PCR). The inflammatory pathway in MH-S cells was determined via western blotting and immunofluorescence (IF) analysis. Finally, the major components of the DIE were identified and separated through ultra-performance liquid chromatography (UPLC) and gas chromatography-mass spectrometry (GC-MS) analysis. Our results showed that the DIE dose-dependently inhibited the CFA-induced NO production in MH-S cells. Moreover, the DIE could suppress the CFA-induced proinflammatory mediators, such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). In addition, the inhibitory effect of the DIE on proinflammatory cytokines, including interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α), was detected with PCR. Moreover, the effect of the DIE on the nuclear factor-κB (NF-κB) pathway in CFA-activated MH-S cells was measured via western blotting. Furthermore, the inhibition of the phosphorylated NF-κB (p-NF-κB) translocation was analyzed using IF assay. The findings of this study indicated that the DIE potentially inhibited the CFA-induced inflammation by blocking the NF-κB inflammatory signaling pathway in MH-S cells and that the DIE might contain favorable anti-inflammatory compounds which may be effective in attenuating lung inflammation.

scholarly journals Mitogen-Activated Protein Kinase Phosphatase 1 Disrupts Proinflammatory Protein Synthesis in Endotoxin-Adapted Monocytes

2013 ◽  
Vol 20 (9) ◽  
pp. 1396-1404 ◽  
Author(s):  
Laura Brudecki ◽  
Donald A. Ferguson ◽  
Charles E. McCall ◽  
Mohamed El Gazzar
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Rna Binding ◽  
Multiorgan Failure ◽  
Mitogen Activated Protein Kinase ◽  
Necrosis Factor Alpha ◽  
Translational Repressor ◽  
Proinflammatory Mediators ◽  
Tnf Α ◽  
Mitogen Activated Protein

ABSTRACTAutotoxic production of proinflammatory mediators during early sepsis induces excessive inflammation, and their later suppression may limit the immune response. We previously reported that sepsis differentially represses transcription and translation of tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β) to reprogram sepsis inflammation. This switch is gene specific and plays a crucial role in the clinically relevant syndrome of endotoxin adaptation/tolerance, multiorgan failure, and poor sepsis outcome. To further define the mechanisms responsible for translation disruption that follows inflammation induction, we used THP-1 human promonocytes as a model of Toll-like receptor 4 (TLR4) responses found in sepsis. We showed that phosphorylation-dependent activation of p38 mitogen-activated protein kinase (MAPK) and translation disruption of TNF-α and IL-6 follow increased MAPK phosphatase 1 (MKP-1) expression and that MKP-1 knockdown rephosphorylates p38 and restores the capacity to translate TNF-α and IL-6 mRNAs. We also observed that the RNA-binding protein motif 4 (RBM4), a p38 MAPK target, accumulates in an unphosphorylated form in the cytosol in endotoxin-adapted cells, suggesting that dephosphorylated RBM4 may function as a translational repressor. Moreover, MKP-1 knockdown promotes RBM4 phosphorylation, blocks its transfer from the nucleus to the cytosol, and reverses translation repression. We also found that microRNA 146a (miR-146a) knockdown prevents and miR-146a transfection induces MKP-1 expression, which lead to increases or decreases in TNF-α and IL-6 translation, respectively. We conclude that a TLR4-, miR-146a-, p38 MAPK-, and MKP-1-dependent autoregulatory pathway regulates the translation of proinflammatory genes during the acute inflammatory response by spatially and temporally modifying the phosphorylation state of RBM4 translational repressor protein.

Chloroquine attenuates lipopolysaccharide-induced inflammatory responses through upregulation of USP25

2017 ◽  
Vol 95 (5) ◽  
pp. 481-491 ◽  
Author(s):  
Changyu Ding ◽  
Fangfang Li ◽  
Yupeng Long ◽  
Jiang Zheng
Keyword(s):  
Macrophage Activation ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Ubiquitin Proteasome System ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Activation Of Transcription ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Ubiquitin Proteasome

Lipopolysaccharide (LPS) is a key pathogenic factor in sepsis, and its recognition by toll-like receptor 4 (TLR4) can activate two district signaling pathways, leading to activation of transcription factors including NF-κB and interferon regulatory factor 3 (IRF3). Chloroquine (CQ) has been shown to affect LPS–TLR4 colocalization and inhibit both MyD88-dependent and TRAM/TRIF-dependent pathways, though the mechanism involved is still poorly understood. Here, we found that the ubiquitin–proteasome system might be involved in this process. CQ increased USP25, a deubiquitinating enzyme, as well as mRNA and protein expression in a dose-dependent manner, which might to some degree be involved in CQ attenuation of LPS-induced macrophage activation. Overexpression of USP25 decreased LPS-induced inflammatory cytokines like TNF-α, IL-6, and IFN-β, while specific siRNA-mediated USP25 silencing increased TNF-α, IL-6, and IFN-β production and secretion. In addition, USP25 deletion strengthened mitogen-activated protein kinase (MAPKs) phosphorylation and IκB degradation. Moreover, USP25 interference increased NF-κB and IRF3 nuclear translocation. Taken together, our data demonstrated a new possible regulator of LPS-induced macrophage activation mediated by CQ, through upregulation of USP25.

scholarly journals 17β-Estradiol Inhibits Inflammatory Gene Expression by Controlling NF-κB Intracellular Localization

2005 ◽  
Vol 25 (8) ◽  
pp. 2957-2968 ◽  
Author(s):  
Serena Ghisletti ◽  
Clara Meda ◽  
Adriana Maggi ◽  
Elisabetta Vegeto
Keyword(s):  
Inflammatory Response ◽  
Intracellular Transport ◽  
Time Course ◽  
Nuclear Translocation ◽  
De Novo ◽  
Intracellular Localization ◽  
Mitogen Activated Protein Kinase ◽  
Proinflammatory Mediators ◽  
17Β Estradiol ◽  
Anti Inflammatory

ABSTRACT Estrogen is an immunoregulatory agent, in that hormone deprivation increases while 17β-estradiol (E2) administration blocks the inflammatory response; however, the underlying mechanism is still unknown. The transcription factor p65/relA, a member of the nuclear factor κB (NF-κB) family, plays a major role in inflammation and drives the expression of proinflammatory mediators. Here we report a novel mechanism of action of E2 in inflammation. We observe that in macrophages E2 blocks lipopolysaccharide-induced DNA binding and transcriptional activity of p65 by preventing its nuclear translocation. This effect is selectively activated in macrophages to prevent p65 activation by inflammatory agents and extends to other members of the NF-κB family, including c-Rel and p50. We observe that E2 activates a rapid and persistent response that involves the activation of phosphatidylinositol 3-kinase, without requiring de novo protein synthesis or modifying Iκ-Bα degradation and mitogen-activated protein kinase activation. Using a time course experiment and the microtubule-disrupting agent nocodazole, we observe that the hormone inhibits p65 intracellular transport to the nucleus. This activity is selectively mediated by estrogen receptor alpha (ERα) and not ERβ and is not shared by conventional anti-inflammatory drugs. These results unravel a novel and unique mechanism for E2 anti-inflammatory activity, which may be useful for identifying more selective ligands for the prevention of the inflammatory response.

scholarly journals Regulation of Proinflammatory Mediators via NF-κB and p38 MAPK-Dependent Mechanisms in RAW 264.7 Macrophages by Polyphenol Components Isolated from KoreaLonicera japonica THUNB

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Kwang-Il Park ◽  
Sang-Rim Kang ◽  
Hyeon-Soo Park ◽  
Do Hoon Lee ◽  
Arulkumar Nagappan ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Nuclear Translocation ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Necrosis Factor Alpha ◽  
Proinflammatory Mediators ◽  
Mapk Activity ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Lonicera japonica THUNB., which abundantly contains polyphenols, has been used as a traditional medicine for thousands of years in East Asian countries because of the anti-inflammation properties. This study aimed to investigate the anti-inflammatory mechanism of polyphenol components isolated from KoreaL. japonica T.by nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) pathway. Polyphenols significantly decreased lipopolysaccharide- (LPS-) induced mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as mRNA expression of tumor necrosis factor-alpha, interleukin- (IL-) 1β, and IL-6. Moreover, polyphenols inhibited nuclear translocation of NF-κB p65, phosphorylation/degradation of the inhibitor ofκB, and phosphorylation of p38 MAPK, whereas the extracellular signal-regulated kinase and Janus N-terminal kinase were not affected. These results indicate that polyphenol components isolated from KoreaL. japonica T.should have anti-inflammatory effect on LPS-stimulated RAW 264.7 cells through the decrease of proinflammatory mediators expression by suppressing NF-κB and p38 MAPK activity.

scholarly journals δ-Tocotrienol, Isolated from Rice Bran, Exerts an Anti-Inflammatory Effect via MAPKs and PPARs Signaling Pathways in Lipopolysaccharide-Stimulated Macrophages

2018 ◽  
Vol 19 (10) ◽  
pp. 3022 ◽  
Author(s):  
Junjun Shen ◽  
Tao Yang ◽  
Youzhi Xu ◽  
Yi Luo ◽  
Xinyue Zhong ◽  
...  
Keyword(s):  
Rice Bran ◽  
Molecular Mechanisms ◽  
Mitogen Activated Protein Kinase ◽  
Peroxisome Proliferator ◽  
Activator Protein 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory ◽  
Inflammatory Effect

δ-Tocotrienol, an important component of vitamin E, has been reported to possess some physiological functions, such as anticancer and anti-inflammation, however their molecular mechanisms are not clear. In this study, δ-tocotrienol was isolated and purified from rice bran. The anti-inflammatory effect and mechanism of δ-tocotrienol against lipopolysaccharides (LPS) activated pro-inflammatory mediator expressions in RAW264.7 cells were investigated. Results showed that δ-tocotrienol significantly inhibited LPS-stimulated nitric oxide (NO) and proinflammatory cytokine (TNF-α, IFN-γ, IL-1β and IL-6) production and blocked the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 (ERK1/2). δ-Tocotrienol repressed the transcriptional activations and translocations of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1), which were closely related with downregulated cytokine expressions. Meanwhile, δ-tocotrienol also affected the PPAR signal pathway and exerted an anti-inflammatory effect. Taken together, our data showed that δ-tocotrienol inhibited inflammation via mitogen-activated protein kinase (MAPK) and peroxisome proliferator-activated receptor (PPAR) signalings in LPS-stimulated macrophages.

scholarly journals Chrysin Derivative CM1 and Exhibited Anti-Inflammatory Action by Upregulating Toll-Interacting Protein Expression in Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1532
Author(s):  
Eui-Baek Byun ◽  
Ha-Yeon Song ◽  
Woo Sik Kim ◽  
Jeong Moo Han ◽  
Ho Seong Seo ◽  
...  
Keyword(s):  
Nuclear Factor Κb ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Tlr Signaling ◽  
Induced Expression ◽  
Interacting Protein ◽  
Proinflammatory Mediators ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Action

Although our previous study revealed that gamma-irradiated chrysin enhanced anti-inflammatory activity compared to intact chrysin, it remains unclear whether the chrysin derivative, CM1, produced by gamma irradiation, negatively regulates toll-like receptor (TLR) signaling. In this study, we investigated the molecular basis for the downregulation of TLR4 signal transduction by CM1 in macrophages. We initially determined the appropriate concentration of CM1 and found no cellular toxicity below 2 μg/mL. Upon stimulation with lipopolysaccharide (LPS), CM1 modulated LPS-stimulated inflammatory action by suppressing the release of proinflammatory mediators (cytokines TNF-α and IL-6) and nitric oxide (NO) and downregulated the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, CM1 markedly elevated the expression of the TLR negative regulator toll-interacting protein (Tollip) in dose- and time-dependent manners. LPS-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II), proinflammatory cytokines (TNF-α and IL-6), COX-2, and iNOS-mediated NO were inhibited by CM1; these effects were prevented by the knockdown of Tollip expression. Additionally, CM1 did not affect the downregulation of LPS-induced expression of MAPKs and NF-κB signaling in Tollip-downregulated cells. These findings provide insight into effective therapeutic intervention of inflammatory disease by increasing the understanding of the negative regulation of TLR signaling induced by CM1.

scholarly journals Marine Microorganism-Derived Macrolactins Inhibit Inflammatory Mediator Effects in LPS-Induced Macrophage and Microglial Cells by Regulating BACH1 and HO-1/Nrf2 Signals through Inhibition of TLR4 Activation

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 656
Author(s):  
Eun-Nam Kim ◽  
Ming Gao ◽  
Hyukjae Choi ◽  
Gil-Saeng Jeong
Keyword(s):  
Culture Broth ◽  
Mitogen Activated Protein Kinase ◽  
Proinflammatory Mediators ◽  
Bv2 Cells ◽  
Mitogen Activated Protein ◽  
Macrolactin A ◽  
Anti Inflammatory ◽  
Pharmacological Potential ◽  
Tlr4 Activation ◽  
Oxide Synthase

Recently, many natural products with unique structure and promising pharmacological potential have been reported from marine-derived microorganisms. The macrolactin A (MA), 15-epi-dihydromacrolactin F (DMF) and macrolactin F (MF) were obtained from the culture broth extract of a marine sediment derived microorganism Bacillus sp. HC001. In this study, MA, DMF and MF inhibited the production and expression of proinflammatory mediators of inducible nitric oxide synthase (iNOS) and cyclooxygenase–2 (COX-2) in LPS-stimulated RAW264.7 and BV2 cells. Also, MA, DMF and MF exert anti-inflammatory effects through the expression of heme oxygenase (HO) -1, a stress-inducing enzyme that converts heme to carbon monoxide (CO), iron and biliberdine. Toll-like receptor 4 (TLR4) expressed by lipopolysaccharide (LPS) was inhibited by increased expression of HO-1 transcription factor Nrf2 and down regulation of BTB Domain And CNC Homolog 1 (BACH1), inhibited phosphorylation of Mitogen-activated protein kinase kinase kinase 7 (MAP3K7, TAK1) and nuclear factor kappaB (NF-κB). These results show that MA, DMF and MF effectively inhibited TLR4 by regulating BACH1 and HO-1/Nrf2 signals in LPS-stimulated RAW264.7 and BV2 cells, which suggests the possibility of use as an anti-inflammatory agent.

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