scholarly journals Neutrophilic Lung Inflammation Suppressed by Picroside II Is Associated with TGF-βSignaling

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Soohwan Noh ◽  
Kyung-Seop Ahn ◽  
Sei-Ryang Oh ◽  
Kyun Ha Kim ◽  
Myungsoo Joo
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Raw 264.7 Cells ◽  
Luciferase Reporter ◽  
Major Constituent ◽  
Inflammatory Factor ◽  
Traditional Herbal Medicine ◽  
Picroside Ii ◽  
Picrorhiza Scrophulariiflora ◽  
Anti Inflammatory

Although acute lung injury (ALI) is a leading cause of death in intensive care unit, effective pharmacologic means to treat ALI patients are lacking. The rhizome ofPicrorhiza scrophulariifloraused in a traditional herbal medicine in Asian countries has been shown to have anti-inflammatory function, and picroside II (PIC II) is known as a major constituent in the plant. Here, we examined whether PIC II has an anti-inflammatory activity, which is applicable for treating ALI. We found that although it is not significantly effective in suppressing proinflammatory factor NF-κB or in activating anti-inflammatory factor Nrf2, PIC II induced the phosphorylation of Smad 2, with concomitant increase of luciferase activity from SBE luciferase reporter in RAW 264.7 cells. H&E staining of lung, differential counting of cells in bronchoalveolar lavage fluid, and semiquantitative RT-PCR analyses of lung tissues show that an intratracheal (i.t.) spraying of PIC II suppressed neutrophilic inflammation and the expression of proinflammatory cytokine genes in the lung, which were elicited by an i.t. LPS instillation to the lung. In addition, PIC II treatment increased the phosphorylation of Smad 2 in the lung tissue. Together, our results suggest that PIC II plays a role as an anti-inflammatory constituent inP. scrophulariiflora, whose activity is associated at least in part with TGF-βsignaling.

scholarly journals Farnesol, a Sesquiterpene Alcohol in Herbal Plants, Exerts Anti-Inflammatory and Antiallergic Effects on Ovalbumin-Sensitized and -Challenged Asthmatic Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Chi-Mei Ku ◽  
Jin-Yuarn Lin
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Peritoneal Macrophages ◽  
Cytokine Secretion ◽  
Dietary Control ◽  
Allergic Asthmatic ◽  
Antiallergic Effect ◽  
Herbal Plants ◽  
Anti Inflammatory ◽  
Necrosis Factor

To investigate the effect of farnesol on allergic asthma, three farnesol doses were extra-added into AIN-76 feed consumed by ovalbumin- (OVA-) sensitized and -challenged mice continuously for 5 weeks, at approximately 5, 25, and 100 mg farnesol/kg, BW/day. The results showed that there were no significant differences in body weight, feed intake, and visceral organ weights between the farnesol supplementation and dietary control groups. Farnesol supplementation decreased interleukin (IL)-6/IL-10 level ratios in bronchoalveolar lavage fluid (BALF). Farnesol supplementation significantly (P<0.05) restored the cytokine secretion ability of peritoneal macrophages that was suppressed as a result of OVA sensitization and challenge and slightly decreased tumor necrosis factor (TNF-α)/IL-10 cytokine secretion ratios. Farnesol supplementation slightly (P>0.05) decreased IL-4 but significantly (P<0.05) increased IL-2 levels secreted by the splenocytes in the presence of OVA, implying that farnesol might have a systemic antiallergic effect on allergic asthmatic mice. Farnesol supplementation significantly (P<0.05) increased IL-10 levels secreted by the splenocytes in the presence of OVA, suggesting that farnesol might have an anti-inflammatory potential to allergic asthmatic mice. Overall, our results suggest that farnesol supplementation may be beneficial to improve the Th2-skewed allergic asthmatic inflammation.

scholarly journals Canscora lucidissima, a Chinese folk medicine, exerts anti-inflammatory activities by inhibiting the phosphorylation of ERK1/2 in LPS-activated macrophages

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiao-ling Fei ◽  
Xiao-yu Zhang ◽  
Rui-juan Qi ◽  
Yun-feng Huang ◽  
Yi-xin Han ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Southern China ◽  
Raw 264.7 Cells ◽  
Luciferase Reporter ◽  
Effective Treatment Option ◽  
Proinflammatory Mediators ◽  
Inflammatory Models ◽  
Inflammatory Mechanism ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Background Canscora lucidissima (Levl. & Vaniot) Hand.-Mazz. (C. lucidissima), mainly distributed in southern China, has been shown to be effective in the treatment of inflammatory diseases. However, the underlying mechanism of its anti-inflammatory effect is not fully understood. Methods In this study, we investigated the anti-inflammatory mechanism of ethanol extract of C. lucidissima (Cl-EE) in lipopolysaccharide (LPS)-induced inflammatory models. ELISA, real-time PCR, Western blot and luciferase reporter assay were used for the experiments in vitro, and ICR mouse endotoxemia model was used for in vivo test. Results Our data showed that Cl-EE reduced the production of NO by down-regulating the mRNA and protein expression of inducible nitric oxide synthase (iNOS) in LPS-activated RAW 264.7 cells. Meanwhile, it potently decreased other proinflammatory mediators, such as TNF-α, IL-6, MCP-1 and IL-1β at the transcriptional and translational levels. Further study indicated that Cl-EE did not affect NF-κB signaling pathway but significantly suppressed the phosphorylation of ERK1/2, rather than JNK or p38. In a LPS-induced endotoxemia mouse model, a single intraperitoneal injection of Cl-EE (75–300 mg/kg) could lower circulatory TNF-α, IL-6 and MCP-1 levels. Conclusions Collectively, our results indicated that Cl-EE suppressed the phosphorylation level of ERK1/2 thus reducing the transcription and translation of inflammatory genes, thereby exerted anti-inflammatory activity. This study reveals the anti-inflammatory mechanism of C. lucidissima and may provide an effective treatment option for a variety of inflammatory diseases.

Paeonol attenuates airway inflammation and hyperresponsiveness in a murine model of ovalbumin-induced asthma

2010 ◽  
Vol 88 (10) ◽  
pp. 1010-1016 ◽  
Author(s):  
Qiang Du ◽  
Gan-Zhu Feng ◽  
Li Shen ◽  
Jin Cui ◽  
Jian-Kang Cai
Keyword(s):  
Bronchoalveolar Lavage ◽  
Airway Inflammation ◽  
Bronchoalveolar Lavage Fluid ◽  
Immunoglobulin E ◽  
Therapeutic Potential ◽  
Lavage Fluid ◽  
Interleukin 4 ◽  
Moutan Cortex ◽  
Ifn Γ ◽  
Anti Inflammatory

Paeonol, the main active component isolated from Moutan Cortex, possesses extensive pharmacological activities such as anti-inflammatory, anti-allergic, and immunoregulatory effects. In the present study, we examined the effects of paeonol on airway inflammation and hyperresponsiveness in a mouse model of allergic asthma. BALB/c mice sensitized and challenged with ovalbumin were administered paeonol intragastrically at a dose of 100 mg/kg daily. Paeonol significantly suppressed ovalbumin-induced airway hyperresponsiveness to acetylcholine chloride. Paeonol administration significantly inhibited the total inflammatory cell and eosinophil count in bronchoalveolar lavage fluid. Treatment with paeonol significantly enhanced IFN-γ levels and decreased interleukin-4 and interleukin-13 levels in bronchoalveolar lavage fluid and total immunoglobulin E levels in serum. Histological examination of lung tissue demonstrated that paeonol significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. These data suggest that paeonol exhibits anti-inflammatory activity in allergic mice and may possess new therapeutic potential for the treatment of allergic bronchial asthma.

scholarly journals Non-Invasive Delivery of Nano-Emulsified Sesame Oil-Extract of Turmeric Attenuates Lung Inflammation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1206
Author(s):  
Sahibzada Tasleem Rasool ◽  
Rajasekhar Reddy Alavala ◽  
Umasankar Kulandaivelu ◽  
Nagaraja Sreeharsha
Keyword(s):  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Lung Inflammation ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Treated Group ◽  
Sesame Oil ◽  
Oil Extract ◽  
Anti Inflammatory ◽  
Nano Emulsion

Turmeric, the golden Indian spice, and the edible oil of sesame seeds are the essential ingredients of Indian food created by ancestors and established the belief of the curative effect of food for many generations. Considering the anti-inflammatory effects of turmeric, we formulated a nano-emulsion of turmeric infused in edible sesame oil, with a globule size of 200–250 nm using high-energy microfluidization. The product with a zeta potential of −11.5 mV showed spherical globules when imaged for scanning and transmission electron microscopy. We explored the anti-inflammatory potential of this edible nano-emulsion in lung inflammation. The lungs are the internal organ most vulnerable to infection, injury, and rapid inflammation from the external environment because of their constant exposure to pollutants, pathogenic microorganisms, and viruses. We evaluated the nano-emulsion for efficacy in ovalbumin-induced lung injury in mice with an oral treatment for two weeks. The therapeutic effect of nano-emulsion of the sesame oil-extract of turmeric was evident from biochemical analysis of bronchoalveolar lavage fluid, lung histopathology, and flow cytometric analysis. The developed nano-emulsion significantly reduced the inflammation and damage to the alveolar network in ovalbumin-injured mice. Significant reduction in the levels of neutrophils and inflammatory cytokines like IL-4, IL-6, and IL-13 in bronchoalveolar lavage fluid was observed in the nano-emulsion-treated group. Leukotriene B4 and IgE were also significantly altered in the treated group, thus suggesting the suitability of the formulation for the treatment of allergy and other inflammatory conditions. The nano-emulsification process potentiated the immunoregulatory effect of turmeric, as observed from the elevated levels of the natural anti-inflammatory cytokine, IL-10. The dietary constituents-based nano-emulsion of spice turmeric helped in scavenging the free radicals in the injured lungs, thus modulating the inflammation pathway. This easily scalable formulation technology approach can therefore serve as a potential noninvasive and safe treatment modality for reducing lung inflammation in lung injury cases.

Abstract 584: Allograft Inflammatory Factor-1 is Required for NfκB Pathway Activity in Macrophages and Atherosclerosis

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Lander Egaña-Gorroño ◽  
Prameladevi Chinnasamy ◽  
Nicholas Sibinga
Keyword(s):  
Oxidized Ldl ◽  
Critical Role ◽  
Immunohistochemical Analysis ◽  
Nuclear Factor Κb ◽  
Raw 264.7 Cells ◽  
Luciferase Reporter ◽  
Inflammatory Factor ◽  
Atherosclerotic Lesions ◽  
Nfκb Pathway

Introduction: In preliminary studies, we found that Allograft inflammatory factor-1 (AIF1) supports MΦ migration, phagocytosis, survival and pro-inflammatory cytokine secretion. Moreover, AIF1 limits necrotic core formation in atherosclerotic lesions in vivo . Nuclear Factor-κB (NFκB)-mediated signal transduction has been established at different stages of atherosclerosis. We hypothesize that AIF1-regulated processes in atherosclerosis may be mediated through effects on NFκB signaling. Methods: Bone marrow (BM) derived MΦs were isolated and immortalized from wt and Aif1 -/- mice and stimulated with oxidized-LDL (50 ug/ul; oxLDL). Lysates were immunoblotted for total and phosphorylated (active) p65 NFκB, and for total and phosphorylated forms of the IκBα repressor. Aif1 expression in mouse Raw 264.7 cells was knocked down (KD) using siRNA, and NFκB reporter activity, measured by a luciferase reporter, was assessed after adding LPS+IFN-γ. Immunohistochemical analysis for phospho-p65 NFκB was performed in atherosclerotic lesions (aortic roots) from Apoe -/- (SKO) and Apoe -/- ;Aif1 -/- (DKO) mice maintained on high fat diet for 16 weeks. Results: In AIF1-deficient BMMΦs stimulated with oxLDL, we found no differences in the levels of total p65 NFκB and IκBα, but interestingly, phospho-p65 NFκB levels were significantly reduced and phospho-IκBα levels increased compared to wt cells (P<0.05). AIF1 KD using siRNA significantly reduced NFκB activity compared to scrambled control (scrambled control vs. AIF1 KD; 40% vs. 22% luciferase activity, P<0.05), and this impairment was rescued with the addition of AIF1 cDNA. In vivo , NFκB phospho-p65 staining showed that in comparison to SKO samples, DKO aortic roots had decreased phospho-p65 NFκB (SKO vs. DKO; 7.0 vs. 4.0 +nuclei/aortic root, P<0.05). Conclusions: AIF1 is required for NFκB activation in MΦs and moreover, AIF1 enhances NFκB activity in atherosclerotic lesions in vivo . Because NFkB has been closely linked to both cytokine expression and cell survival signaling, these results point to a critical role for AIF1 in pro-inflammatory MΦ functions. Future studies involve identifying the precise steps of the pathway controlled by AIF1, and the mechanisms by which AIF1 affects NFκB signaling.

scholarly journals Melatonin Alleviates Radiation-Induced Lung Injury via Regulation of miR-30e/NLRP3 Axis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Xu Wu ◽  
Haiying Ji ◽  
Yuli Wang ◽  
Chenlin Gu ◽  
Wenyu Gu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Nlrp3 Inflammasome ◽  
Intraperitoneal Administration ◽  
Lavage Fluid ◽  
Raw 264.7 Cells ◽  
Luciferase Reporter ◽  
Pcr Analysis ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
Radiation Induced

Melatonin is a well-known anti-inflammatory and antioxidant molecule, which plays a crucial role in various physiological functions. In this study, mice received a single dose of 15 Gy radiation delivered to the lungs and daily intraperitoneal administration of melatonin. After 7 days, mice were processed to harvest either bronchoalveolar lavage fluid for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that melatonin markedly alleviated the oxidative stress and injury, especially suppressing the infiltration of macrophages (CD11b+CD11c−) and neutrophils (CD11b+Ly6G+) to the irradiated lungs. Moreover, in the irradiated RAW 264.7 cells, melatonin blocked the NLRP3 inflammasome activation accompanied with the inhibition of the IL-1β release and caspase-1 activity. However, melatonin restored the downregulated miR-30e levels. Quantitative PCR analysis of miR-30e and NLRP3 indicated the negative correlation between them. Notably, immunofluorescence staining showed that overexpression of miR-30e dramatically diminished the increased NLRP3 expression. Luciferase reporter assay confirmed that NLRP3 was a target gene of miR-30e. Western blotting revealed that transfection with miR-30e mimics markedly reduced the expressions of NLRP3 and cleaved caspase-1, whereas this phenomenon was reversed by the miR-30e inhibitor. Consistent with this, the beneficial effect of melatonin under irradiated exposure was blunted in cells transfected with anti-miR-30e. Collectively, our results demonstrate that the NLRP3 inflammasome contributed to the pathogenesis of radiation-induced lung injury. Meanwhile, melatonin exerted its protective effect through negatively regulating the NLRP3 inflammasome in macrophages. The melatonin-mediated miR-30e/NLRP3 signaling may provide novel therapeutic targets for radiation-induced injury.

scholarly journals Protective Effect of the Fruit Hull ofGleditsia sinensison LPS-Induced Acute Lung Injury Is Associated with Nrf2 Activation

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jun-Young Choi ◽  
Min Jung Kwun ◽  
Kyun Ha Kim ◽  
Ji Hyo Lyu ◽  
Chang Woo Han ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Inflammation ◽  
Therapeutic Option ◽  
Raw 264.7 Cells ◽  
Inflammatory Factor ◽  
Tnf Α ◽  
Reporter Assays ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

The fruit hull ofGleditsia sinensis(FGS) has been prescribed as a traditional eastern Asian medicinal remedy for the treatment of various respiratory diseases, but the efficacy and underlying mechanisms remain poorly characterized. Here, we explored a potential usage of FGS for the treatment of acute lung injury (ALI), a highly fatal inflammatory lung disease that urgently needs effective therapeutics, and investigated a mechanism for the anti-inflammatory activity of FGS. Pretreatment of C57BL/6 mice with FGS significantly attenuated LPS-induced neutrophilic lung inflammation compared to sham-treated, inflamed mice. Reporter assays, semiquantitative RT-PCR, and Western blot analyses show that while not affecting NF-κB, FGS activated Nrf2 and expressed Nrf2-regulated genes including GCLC, NQO-1, and HO-1 in RAW 264.7 cells. Furthermore, pretreatment of mice with FGS enhanced the expression of GCLC and HO-1 but suppressed that of proinflammatory cytokines in including TNF-α and IL-1β in the inflamed lungs. These results suggest that FGS effectively suppresses neutrophilic lung inflammation, which can be associated with, at least in part, FGS-activating anti-inflammatory factor Nrf2. Our results suggest that FGS can be developed as a therapeutic option for the treatment of ALI.

scholarly journals Anti-inflammatory Activity of Lefamulin in a Lipopolysaccharide-Induced Lung Neutrophilia Model

2020 ◽  
Author(s):  
Michael Hafner ◽  
Susanne Paukner ◽  
Wolfgang W. Wicha ◽  
Boška Hrvačić ◽  
Steven P. Gelone
Keyword(s):  
Bacterial Pneumonia ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Inflammatory Activity ◽  
Free Base ◽  
Cell Counts ◽  
Oral Dexamethasone ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Neutrophil Cell

ABSTRACTLefamulin is a novel pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia. This study demonstrated anti-inflammatory activity of lefamulin in a murine lipopolysaccharide-induced lung neutrophilia model. Pretreatment of mice at clinically relevant lefamulin subcutaneous doses (35, 70, 140 mg/kg [free base]) followed by intranasal lipopolysaccharide challenge (5 μg/50 μL/mouse) demonstrated significant, dose-dependent reductions in total and neutrophil cell counts in bronchoalveolar lavage fluid samples, with reductions comparable to oral dexamethasone (0.5 mg/kg) pretreatment.

Immunoregulatory effects of regulated, lung-targeted expression of IL-10 in vivo

2005 ◽  
Vol 288 (2) ◽  
pp. L251-L265 ◽  
Author(s):  
Donn Spight ◽  
Bin Zhao ◽  
Michael Haas ◽  
Susan Wert ◽  
Alvin Denenberg ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Inflammation ◽  
Lavage Fluid ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Targeted Expression ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

Regulation of pulmonary inflammation involves an intricate balance of both pro- and anti-inflammatory mediators. Acute lung injury can result from direct pulmonary insults that activate alveolar macrophages to respond with increased cytokine expression. Such cytokine gene expression is mediated in part via NF-κB. IL-10 has been previously identified as an important endogenous anti-inflammatory cytokine in vivo on the basis of inhibiting NF-κB activation; however, the mechanism of this inhibition remains incompletely defined. We hypothesized that IL-10 regulated NF-κB activation in vivo via IκK inhibition. A bitransgenic mouse that allowed for externally regulated, lung-specific human IL-10 overexpression was generated. In the bitransgenic mice, introduction of doxycycline induced lung-specific, human IL-10 overexpression. Acute induction of IL-10 resulted in significant decreases in bronchoalveolar lavage fluid neutrophils (48%, P = 0.03) and TNF (62%, P < 0.01) following intratracheal LPS compared with bitransgenic negative mice. In vitro kinase assays showed this decrease to correlate to diminished lung IκK activity. Furthermore, we also examined the effect of chronic IL-10 overexpression in these transgenic mice. Results show that IL-10 overexpression in lungs of mature mice increased the number of intrapulmonary cells the phenotype of which was skewed toward increased B220+/CD45+ B cells and CD4+ T cells and was associated with increased CC chemokine expression. Thus regulated, lung-specific IL-10 overexpression may have a variety of complex immunologic effects depending on the timing and duration of expression.

scholarly journals Nuciferine Inhibits Proinflammatory Cytokines via the PPARs in LPS-Induced RAW264.7 Cells

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2723 ◽  
Author(s):  
Chao Zhang ◽  
Jianjun Deng ◽  
Dan Liu ◽  
Xingxia Tuo ◽  
Yan Yu ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Raw 264.7 Cells ◽  
Luciferase Reporter ◽  
Raw 264.7 ◽  
Peroxisome Proliferator ◽  
Reporter Assay ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tnf Α ◽  
Natural Alkaloid ◽  
Anti Inflammatory

Inflammation is important and has been found to be an underlying cause in many acute and chronic human diseases. Nuciferine, a natural alkaloid containing an aromatic ring, is found in the nelumbo nucifera leaves. It has been shown to have potential anti-inflammatory activities, but the molecular mechanism has remained unclear. In this study, we found that nuciferine (10 μM) significantly inhibited the lipopolysaccharide (LPS)-induced inflammatory cytokine IL-6 and TNF-α production in RAW 264.7 cells. In addition, the luciferase reporter assay results of different subtypes of the peroxisome proliferator-activated receptor (PPAR) showed that nuciferine dose-dependently activated all the PPAR activities. Specific inhibitors of PPARα and PPARγ significantly abolished the production of inflammatory cytokines as well as IκBα degradation. However, PPARδ inhibitor did not show this effect. Our results suggested a potential molecular mechanism of the anti-inflammatory effects of nuciferine in LPS-induced inflammation, at least in part, by activating PPARα and PPARγ in RAW 264.7 cells.

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