Anti-inflammatory effects of resveratrol occur via inhibition of lipopolysaccharide-induced NF-κB activation in Caco-2 and SW480 human colon cancer cells

Resveratrol, a polyphenol abundantly found in grapes and red wine, exhibits beneficial health effects due to its anti-inflammatory properties. In the present study, we evaluated the effect of resveratrol on inflammatory responses induced by lipopolysaccharide (LPS) treatment of human intestinal Caco-2 and SW480 cell lines. In the LPS-treated intestinal cells, resveratrol dose-dependently inhibited the expression of inducible NO synthase (iNOS) mRNA as well as protein expression, resulting in a decreased production of NO. In addition, Toll-like receptor-4 expression was significantly diminished in LPS-stimulated cells after resveratrol pre-treatment. To investigate the mechanisms by which resveratrol reduces NO production and iNOS expression, we examined the activation of inhibitor of κB (IκB) in LPS-stimulated intestinal cells. Results demonstrated that resveratrol inhibited the phosphorylation, as well as the degradation, of the IκB complex. Overall, these results show that resveratrol is able to reduce LPS-induced inflammatory responses by intestinal cells, interfering with the activation of NF-κB-dependent molecular mechanisms.

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Histatin-1 Attenuates LPS-Induced Inflammatory Signaling in RAW264.7 Macrophages

International Journal of Molecular Sciences ◽

10.3390/ijms22157856 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7856

Author(s):

Sang Min Lee ◽

Kyung-No Son ◽

Dhara Shah ◽

Marwan Ali ◽

Arun Balasubramaniam ◽

...

Keyword(s):

Molecular Mechanisms ◽

Cytokine Production ◽

Inflammatory Responses ◽

Critical Role ◽

Mapk Signaling ◽

Response To Treatment ◽

No Production ◽

Inflammatory Signaling ◽

Raw264.7 Macrophages ◽

Inflammatory Mediator Production

Macrophages play a critical role in the inflammatory response to environmental triggers, such as lipopolysaccharide (LPS). Inflammatory signaling through macrophages and the innate immune system are increasingly recognized as important contributors to multiple acute and chronic disease processes. Nitric oxide (NO) is a free radical that plays an important role in immune and inflammatory responses as an important intercellular messenger. In addition, NO has an important role in inflammatory responses in mucosal environments such as the ocular surface. Histatin peptides are well-established antimicrobial and wound healing agents. These peptides are important in multiple biological systems, playing roles in responses to the environment and immunomodulation. Given the importance of macrophages in responses to environmental triggers and pathogens, we investigated the effect of histatin-1 (Hst1) on LPS-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 (RAW) macrophages. LPS-induced inflammatory signaling, NO production and cytokine production in macrophages were tested in response to treatment with Hst1. Hst1 application significantly reduced LPS-induced NO production, inflammatory cytokine production, and inflammatory signaling through the JNK and NF-kB pathways in RAW cells. These results demonstrate that Hst1 can inhibit LPS-induced inflammatory mediator production and MAPK signaling pathways in macrophages.

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Anti-Inflammatory Effect of Buckwheat Sprouts in Lipopolysaccharide-Activated Human Colon Cancer Cells and Mice

Bioscience Biotechnology and Biochemistry ◽

10.1271/bbb.80324 ◽

2008 ◽

Vol 72 (12) ◽

pp. 3148-3157 ◽

Cited By ~ 30

Author(s):

Satoshi ISHII ◽

Takafumi KATSUMURA ◽

Chikara SHIOZUKA ◽

Keisuke OOYAUCHI ◽

Kunito KAWASAKI ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Human Colon ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Anti Inflammatory ◽

Human Colon Cancer Cells ◽

Inflammatory Effect

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Abstract 153: Bile Acid Receptor TGR5 Agonism Represents Anti-inflammatory Effects via Stimulating Nitric Oxide Production in Vascular Endothelial Cells

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.32.suppl_1.a153 ◽

2012 ◽

Vol 32 (suppl_1) ◽

Author(s):

Taiki Kida ◽

Yoshiki Tsubosaka ◽

Masatoshi Hori ◽

Hiroshi Ozaki ◽

Takahisa Murata

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Bile Acids ◽

Inflammatory Responses ◽

Vascular Endothelial Cells ◽

Lithocholic Acid ◽

Signal Pathways ◽

No Production ◽

Vascular Endothelial ◽

Anti Inflammatory

Objective TGR5, a membrane-bound, G-protein-coupled receptor for bile acids, is known to be involved in regulation of energy homeostasis and inflammation. However, little is known about the function of TGR5 in vascular endothelial cells. In the present study, we examined whether TGR5 agonism represents anti-inflammatory effects in vascular endothelial cells focusing on nitric oxide (NO) production. Methods and Results In human umbilical vein endothelial cells (HUVECs), treatment with taurolithocholic acid (TLCA), which has the highest affinity to TGR5 among various bile acids, significantly reduced tumor necrosis factor (TNF)-α-induced vascular cell adhesion molecule (VCAM)-1 protein expression and adhesion of human monocytes, U937. These effects were abrogated by a NO synthase (NOS) inhibitor, N G -Monomethyl-L-arginine (L-NMMA). In bovine aortic endothelial cells (BAECs), treatment with TLCA as well as lithocholic acid, which also has high affinity to TGR5, significantly increased the NO production. In contrast, deoxycholic acid and chenodeoxycholic acid, which possess low affinity to TGR5, did not affect the NO production. Gene depletion of TGR5 by siRNA transfection abolished TLCA-induced NO production in BAECs. TLCA-induced NO production was also observed in HUVECs measured as intracellular cGMP accumulation. We next investigated the signal pathways responsible for the TLCA-induced NO production in endothelial cells. Treatment with TLCA increased endothelial NOS (eNOS) ser1177 phosphorylation in HUVECs. This response was accompanied by increased Akt ser473 phosphorylation and intracellular Ca 2+ ([Ca 2+ ] i ). Treatment with phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or blockade of calcium channel with La 3+ , significantly decreased TLCA-induced eNOS ser1177 phosphorylation and subsequent NO production. Conclusion These results indicate that TGR5 agonism can mediate anti-inflammatory responses by suppressing VCAM-1 expression and monocytes adhesion to endothelial cells. This function is dependent on NO production via Akt activation and [Ca 2+ ] i increase.

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Abstract 620: Angiotensin AT2 Receptor Exerts an Anti-inflammatory Response in Lipopolysaccharide-activated THP-1 Macrophages

Hypertension ◽

10.1161/hyp.62.suppl_1.a620 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Isha S Dhande ◽

Tahir Hussain

Keyword(s):

Inflammatory Response ◽

Interleukin 10 ◽

Receptor Expression ◽

Human Macrophage ◽

No Production ◽

At2 Receptor ◽

Tnf Α ◽

Anti Inflammatory ◽

Pre Treatment ◽

Lps Activation

Macrophages have been shown to be an important contributor to the pathogenesis of hypertension and stroke. The angiotensin AT2 receptor (AT2R), which is expressed in macrophages, is known to promote vasodialation, natriuresis and lower inflammation. The goal of the present study was to explore the anti-inflammatory role of AT2R stimulation in human macrophage-like THP-1 cells activated by lipopolysaccharide (LPS). Phorbol 12-myristate 13-acetate (PMA) differentiated macrophage-like THP-1 cells were treated with AT2R agonist C21 (1 μmol/L) for 30 minutes prior to activation with LPS (1 μg/ml). Media and cells were collected after 24 hours and were analyzed for levels of pro- and anti-inflammatory cytokines and proteins. Pre-treatment with C21 resulted in a 4-fold increase (104.8±6.1 vs 406.7±52.3) in anti-inflammatory interleukin-10 (IL-10) production and a 5-fold decrease (3560±237 vs 588.8±15.94) in pro-inflammatory tumor necrosis factor-α (TNF-α) levels in the media in response to LPS. Predictably, LPS resulted in a 6-fold up-regulation of iNOS expression which was prevented with C21 pre-treatment. A modest decrease in the anti-inflammatory macrophage mannose receptor C type 2 (MRC2) expression was detected with LPS treatment. AT2R agonist pre-treatment, however, increased this receptor expression by ~70% after LPS activation. C21 alone also resulted in a 20% increase in MRC2 expression compared to untreated controls. The anti-inflammatory effect of AT2R activation was abolished in the presence of neutralizing IL-10 antibody (1 μg/ml), indicating a central role for IL-10 in mediating the beneficial response to C21 in LPS activated macrophages. Further, inhibition of nitric oxide (NO) by L-NAME prior to C21 pre-treatment also prevented the decrease in TNF-α and increase in IL-10 in response to AT2R agonist, which suggests that the anti-inflammatory response to C21 may be mediated via increase in NO production prior to LPS activation of macrophages. In conclusion, AT2R stimulation may potentially suppress the inflammatory response of macrophages to LPS by shifting the balance from pro- to anti-inflammatory cytokine production and may prove to be beneficial in the control of the inflammatory component of stroke and hypertension.

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Structure-Dependent Effects of Bisphosphonates on Inflammatory Responses in Cultured Neonatal Mouse Calvaria

Antioxidants ◽

10.3390/antiox9060503 ◽

2020 ◽

Vol 9 (6) ◽

pp. 503

Author(s):

Keiko Suzuki ◽

Sadaaki Takeyama ◽

Shinobu Murakami ◽

Masahiro Nagaoka ◽

Mirei Chiba ◽

...

Keyword(s):

Nuclear Translocation ◽

Inflammatory Responses ◽

Bone Diseases ◽

Neonatal Mouse ◽

Side Chain ◽

Inos Mrna ◽

No Production ◽

Tyrosine Nitration ◽

Mouse Calvaria ◽

Neonatal Mouse Calvaria

Bisphosphonates (BPs) are classified into two groups, according to their side chain structures, as nitrogen-containing BPs (NBPs) and non-nitrogen-containing BPs (non-NBPs). In this study, we examined the effects of NBPs and non-NBPs on inflammatory responses, by quantifying the inflammatory mediators, prostaglandin E2 (PGE2) and nitric oxide (NO), in cultured neonatal mouse calvaria. All examined NBPs (pamidronate, alendronate, incadronate, risedronate, zoledronate) stimulated lipopolysaccharide (LPS)-induced PGE2 and NO production by upregulating COX-2 and iNOS mRNA expression, whereas non-NBPs (etidronate, clodronate, tiludronate) suppressed PGE2 and NO production, by downregulating gene expression. Additionally, [4-(methylthio) phenylthio] methane bisphosphonate (MPMBP), a novel non-NBP with an antioxidant methylthio phenylthio group in its side chain, exhibited the most potent anti-inflammatory activity among non-NBPs. Furthermore, results of immunohistochemistry showed that the nuclear translocation of NF-κB/p65 and tyrosine nitration of cytoplasmic protein were stimulated by zoledronate, while MPMBP inhibited these phenomena, by acting as a superoxide anion (O2−) scavenger. These findings indicate that MPMBP can act as an efficacious agent that causes fewer adverse effects in patients with inflammatory bone diseases, including periodontitis and rheumatoid arthritis.

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Basal anti-inflammatory responses in cultured endothelial cells exposed to two conjugated linoleic acids

Proceedings of The Nutrition Society ◽

10.1017/s0029665120004310 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Carina Valenzuela ◽

Elizabeth Miles ◽

Philip Calder

Keyword(s):

Inflammatory Responses ◽

Adhesion Assay ◽

Dependent Manner ◽

Relative Expression ◽

Inflammatory Pathways ◽

Expression Of Genes ◽

Low Concentrations ◽

Genes Encoding ◽

Anti Inflammatory ◽

Pre Treatment

AbstractConjugated linoleic acid (CLA) isomers have been shown to possess anti-atherosclerotic properties, which may be related to the downregulation of inflammatory pathways. Whether low concentrations of CLAs are able to affect basal, unstimulated endothelial cell (EC) responses is not clear. The aim of this study was to evaluate the effects of two CLAs (cis-9, trans-11 and trans-10, cis-12) on basal inflammatory responses by ECs.EA.hy926 cells (HUVEC lineage) were cultured under standard conditions and exposed to CLAs (1 and 10 μM) for 48 hours. MTT assay was performed to determine cell viability; incorporation of FA was confirmed by gas chromatography; inflammatory mediators were assessed by multiplex immunoassay; the relative expression of genes encoding transcription factors and inflammatory cytokines was assessed through real-time PCR and static adhesion assay was used to evaluate monocyte attachment to the EC monolayer.CLAs were incorporated into ECs in a dose-dependent manner. Pre-treatment with CLA9,11 (1 uM) significantly reduced unstimulated, basal concentrations of MCP-1 (p < 0.05), and CLA10,12 at 10 uM had the same effect (p < 0.05). Both CLAs at 10 uM increased the relative expression of NFκβ (p < 0.01 and p < 0.05, respectively), while decreasing the relative expression of PPARα (p < 0.0001), COX-2 (p < 0.0001) and IL-6 (p < 0.0001). In contrast, no effect was observed in the adhesion assay for either CLA.These results suggest that both CLAs at a low concentration have a neutral or modest anti-inflammatory effect in basal conditions, which may influence endothelial function and risk of vascular disease. Interestingly, at these low CLA concentrations some pro-inflammatory genes are upregulated while others are down regulated. This suggests complex effects of CLAs on inflammatory pathways.

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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 ◽

10.3390/foods8110582 ◽

2019 ◽

Vol 8 (11) ◽

pp. 582 ◽

Cited By ~ 5

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.

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Ethanol Extract of Lilium Bulbs Plays an Anti-Inflammatory Role by Targeting the IKKα/β-Mediated NF-κB Pathway in Macrophages

The American Journal of Chinese Medicine ◽

10.1142/s0192415x18500672 ◽

2018 ◽

Vol 46 (06) ◽

pp. 1281-1296 ◽

Cited By ~ 9

Author(s):

Sang Yun Han ◽

Young-Su Yi ◽

Seong-Gu Jeong ◽

Yo Han Hong ◽

Kang Jun Choi ◽

...

Keyword(s):

Nitric Oxide ◽

Signaling Pathway ◽

Nuclear Translocation ◽

Inflammatory Responses ◽

Inflammatory Activity ◽

Raw264.7 Cells ◽

No Production ◽

Dependent Manner ◽

Bioactive Components ◽

Anti Inflammatory

Lilium bulbs have long been used as Chinese traditional medicines to alleviate the symptoms of various human inflammatory diseases. However, mechanisms of Lilium bulb-mediated anti-inflammatory activity and the bioactive components in Lilium bulbs remain unknown. In the present study, the anti-inflammatory activity of Lilium bulbs and the underlying mechanism of action were investigated in macrophages using Lilium bulb ethanol extracts (Lb-EE). In a dose-dependent manner, Lb-EE inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and bone marrow-derived macrophages (BMDMs) without causing significant cytotoxicity. Lb-EE also down-regulated mRNA expression of inflammatory genes in LPS-stimulated RAW264.7 cells, which included inducuble nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]). Furthermore, Lb-EE markedly restored LPS-induced morphological changes in RAW264.7 cells to a normal morphology. HPLC analysis identified quercetin, luteolin, and kaempferol as bioactive components contained in Lb-EE. Mechanistic studies in LPS-stimulated RAW264.7 cells revealed that Lb-EE suppressed MyD88- and TRIF-induced NF-[Formula: see text]B transcriptional activation and the nuclear translocation of NF-[Formula: see text]B transcription factors. Moreover, Lb-EE inhibited IKK[Formula: see text]/[Formula: see text]-induced activation of the NF-[Formula: see text]B signaling pathway and IKK inhibition significantly reduced NO production in LPS-stimulated RAW264.7 cells. Taken together, these results suggest that Lb-EE plays an anti-inflammatory role by targeting IKK[Formula: see text]/[Formula: see text]-mediated activation of the NF-[Formula: see text]B signaling pathway during macrophage-mediated inflammatory responses.

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