Potential antimicrobial effects of human lactoferrin against oral infection with Listeria monocytogenes in mice

2005 ◽  
Vol 54 (11) ◽  
pp. 1049-1054 ◽  
Author(s):  
Hui-Young Lee ◽  
Jong-Hwan Park ◽  
Seung-Hyeok Seok ◽  
Min-Won Baek ◽  
Dong-Jae Kim ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Inflammatory Cytokines ◽  
Oral Infection ◽  
Human Lactoferrin ◽  
Histopathological Analysis ◽  
Mrna Levels ◽  
Antimicrobial Effects ◽  
Bacterial Enumeration

Listeria monocytogenes is a food-borne pathogen that causes serious listeriosis in humans. Antimicrobial effects of human lactoferrin (hLF) against L. monocytogenes have been clearly demonstrated in in vitro studies. However, in vivo studies have not been reported yet. This study investigated whether the oral administration of hLF could inhibit oral infection of listeria in BALB/c mice. The MICs for several strains of L. monocytogenes were determined, and the most sensitive strain was used for the animal work. hLF was administered to BALB/c mice for 7 days, commencing 4 days before oral infection. The effect of hLF was determined by bacterial enumeration and histopathological analysis of the liver and spleen, which are well-known as the major targets of oral listeria infection in mice. In bacterial enumeration, hLF decreased the number of L. monocytogenes cells in the liver. Histopathologically, the size and frequency of necrotic foci in the liver samples decreased with hLF administration. However, these changes were not observed in the spleen samples. The mRNA levels of inflammatory cytokines, such as interleukin (IL)-1β, tumour necrosis factor (TNF)-α and interferon (IFN)-γ, decreased in the liver of mice receiving hLF. This study has shown that hLF decreases the hepatic colonization of L. monocytogenes, hepatic necrosis and expression of inflammatory cytokines. It revealed that perorally given hLF could mediate antimicrobial and anti-inflammatory activities remote from the gut (i.e. in the liver) of mice challenged with L. monocytogenes.

scholarly journals Interleukin-15 May Be Responsible for Early Activation of Intestinal Intraepithelial Lymphocytes after Oral Infection with Listeria monocytogenes in Rats

1998 ◽  
Vol 66 (12) ◽  
pp. 5677-5683 ◽  
Author(s):  
Kenji Hirose ◽  
Hirohiko Suzuki ◽  
Hitoshi Nishimura ◽  
Akio Mitani ◽  
Junji Washizu ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
Oral Infection ◽  
Epithelial Cell Line ◽  
Intestinal Intraepithelial Lymphocytes ◽  
Interleukin 15 ◽  
Ifn Γ

ABSTRACT Exogenous interleukin-15 (IL-15) stimulates intestinal intraepithelial lymphocytes (i-IEL) from mice to proliferate and produce gamma interferon (IFN-γ) in vitro. To determine whether endogenous IL-15 is involved in activation of i-IEL during intestinal infection, we examined IL-15 synthesis by intestinal epithelial cells (i-EC) after infection with Listeria monocytogenes in rats. In in vitro experiments, invasion of L. monocytogenes into IEC-6 cells, a rat small intestine epithelial cell line, evidently induced IL-15 mRNA expression coincident with nuclear factor κB (NF-κB) activation, which is essential for IL-15 gene expression. IL-15 synthesis was detected in rat i-EC on day 1 after an oral inoculation of L. monocytogenes in vivo. The numbers of T-cell receptor (TCR) γδ+ T cells, NKR.P1+cells, and CD3+ CD8+ αα cells in i-IEL were significantly increased on day 1 after oral infection. The i-IEL from infected rats produced larger amounts of IFN-γ upon stimulation with immobilized anti-TCR γδ or anti-NKR.P1 monoclonal antibodies. These results suggest that IL-15 produced by i-EC may stimulate significant fractions of i-IEL to produce IFN-γ at an early phase of oral infection with L. monocytogenes.

Pro-inflammatory cytokine and apoptotic gene mRNA levels against lentogenic and velogenic Newcastle disease virus pathotypes in in-vivo and in-vitro biological systems

2018 ◽  
Author(s):  
Ranjani Rajasekaran ◽  
J. John Kirubaharan ◽  
M. Vidhya ◽  
P. Shilpa and N. Daniel Joy Chandran
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Clinical Signs ◽  
Mrna Levels ◽  
Cytokine Mrna ◽  
Apoptotic Gene ◽  
Pro Inflammatory Cytokines ◽  
Gene Mrna

Knowledge on the influence of pro-inflammatory cytokine and apoptotic gene mRNA levels in the pathogenesis of Indian field isolates of Newcastle disease virus (NDV) is little. In this study, cytokine mRNA levels were elucidated in spleen of chickens (in-vivo) and chicken embryo fibroblast cells (in-vitro) infected with lentogenic D58 strain and viscerotropic velogenic D165 isolate until five days post infection (dpi). In spleen of chickens infected with D165, maximum upregulation of pro-inflammatory cytokines (IL-1b, IL-6, TNF-a), chemokine (IL-8) and apoptotic gene (Caspase-8) at 3dpi correlated with the onset of severe clinical signs and necrotic histopathological lesions in spleen, proventriculus, intestine and caecal tonsil of chickens. Similarly, in CEF cells infected with D165, upregulation of pro-inflammatory cytokine and apoptotic gene mRNA levels correlated with the appearance of CPE. In spleen of chickens and CEF cells infected with D58, there was comparatively minimal upregulation of pro-inflammatory cytokine and apoptotic gene mRNA levels which did not cause histopathological changes in tissues and CPE formation in CEF cells. In both in-vivo and in-vitro systems, upregulation of anti-inflammatory cytokine IL-10 showed inhibitory effects on the mRNA levels of pro-inflammatory cytokines. Thus, this study reports variation in the cytokine mRNA levels elucidated in response to two different pathotypes isolated from India and associates the same with the clinical signs and pathological lesions produced during the course of ND. 

scholarly journals Polyphenols Derived from Lychee Seed Suppress Aβ (1-42)-Induced Neuroinflammation

2018 ◽  
Vol 19 (7) ◽  
pp. 2109 ◽  
Author(s):  
Yong Tang ◽  
Rui Xiong ◽  
An-Guo Wu ◽  
Chong-Lin Yu ◽  
Ya Zhao ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Protein Expression ◽  
Inflammatory Cytokines ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Future Research ◽  
Mrna Levels ◽  
Bax Protein

Amyloid-β (Aβ) is commonly recognized as the most important factor that results in neuronal cell death and accelerates the progression of Alzheimer’s disease (AD). Increasing evidence suggests that microglia activated by Aβ release an amount of neurotoxic inflammatory cytokines that contribute to neuron death and aggravate AD pathology. In our previous studies, we found that lychee seed fraction (LSF), an active fraction derived from the lychee seed, could significantly improve the cognitive function of AD rats and inhibit Aβ-induced neuroinflammation in vitro, and decrease neuronal injuries in vivo and in vitro. In the current study, we aimed to isolate and identify the specific components in LSF that were responsible for the anti-neuroinflammation effect using preparative high performance liquid chromatography (pre-HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) methods. To this end, we confirmed two polyphenols including catechin and procyanidin A2 that could improve the morphological status of BV-2 cells and suppress the release, mRNA levels, and protein expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) through downregulating the nuclear factor-κB (NF-κB) signaling pathway using ELISA, RT-PCR, and Western blotting methods. Furthermore, catechin and procyanidin A2 could inhibit Aβ-induced apoptosis in BV-2 cells by upregulating Bcl-2 and downregulating Bax protein expression. Therefore, the current study illustrated the active substances in lychee seed, and first reported that catechin and procyanidin A2 could suppress neuroinflammation in Aβ-induced BV-2 cells, which provides detailed insights into the molecular mechanism of catechin and procyanidin A2 in the neuroprotective effect, and their further validations of anti-neuroinflammation in vivo is also essential in future research.

scholarly journals Deacetyl Ganoderic Acid F Inhibits LPS-Induced Neural Inflammation via NF-κB Pathway Both In Vitro and In Vivo

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 85 ◽  
Author(s):  
Feiya Sheng ◽  
Lele Zhang ◽  
Songsong Wang ◽  
Lele Yang ◽  
Peng Li
Keyword(s):  
Inflammatory Cytokines ◽  
Nuclear Translocation ◽  
Therapeutic Potential ◽  
Serum Levels ◽  
No Production ◽  
Mrna Levels ◽  
Mice Model ◽  
Ganoderic Acid

Microglia mediated neuronal inflammation has been widely reported to be responsible for neurodegenerative disease. Deacetyl ganoderic acid F (DeGA F) is a triterpenoid isolated from Ganoderma lucidum, which is a famous edible and medicinal mushroom used for treatment of dizziness and insomnia in traditional medicine for a long time. In this study the inhibitory effects and mechanisms of DeGA F against lipopolysaccharide (LPS)-induced inflammation both in vitro and in vivo were investigated. On murine microglial cell line BV-2 cells, DeGA F treatment inhibited LPS-triggered NO production and iNOS expression and affected the secretion and mRNA levels of relative inflammatory cytokines. DeGA F inhibited LPS-induced activation of the NF-κB pathway, as evidenced by decreased phosphorylation of IKK and IκB and the nuclear translocation of P65. In vivo, DeGA F treatment effectively inhibited NO production in zebrafish embryos. Moreover, DeGA F suppressed the serum levels of pro-inflammatory cytokines, including TNF-α and IL-6 in LPS-stimulated mice model. DeGA F reduced inflammatory response by suppressing microglia and astrocytes activation and also suppressed LPS-induced NF-κB activation in mice brains. Taken together, DeGA F exhibited remarkable anti-inflammatory effects and promising therapeutic potential for neural inflammation associated diseases.

scholarly journals Bullatine a Exerted Anti-Inflammatory Effects by Inhibiting JNK/ROS/NF-κB Pathway and Attenuates Systemic Inflammatory Response in LPS-Challenged Mice

2021 ◽  
Author(s):  
Shuhan Liu ◽  
Meichen Yan ◽  
Yajin Liao ◽  
Yong Cheng
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Nuclear Translocation ◽  
Ros Generation ◽  
Mrna Levels ◽  
Iκb Kinase ◽  
Inflammatory Mechanism ◽  
Anti Inflammatory

Abstract Background: The genus Aconitum has rich pharmacological characteristics. Aconiti brachypodi Radix (Xue-shang-yi-zhi-hao) is a dried root of aconitum, which is considered to be analgesic and anti-inflammatory in modern medical and pharmaceutical clinical studies. Bullatine A (BA), a major active ingredient of this plant, has been reported for its significant anti-analgesic effect in previous studies. However, the role of BA in inflammation is unknown. In the current study, we aimed to explore the effect of BA on lipopolysaccharide (LPS)-induced inflammatory response both in vitro and in vivo and its potential anti-inflammatory mechanism.Materials and Methods: The anti-inflammatory effect of BA was evaluated in two different types of LPS-induced macrophages, including BV-2 microglial cells and immortalized murine bone marrow-derived macrophages (iBMDMs), and in acute inflammation mouse models induced by LPS. Immunofluorescence, flow cytometry, quantitative RT-PCR, western blot and Hematoxylin-Eosin staining were used to determine the anti-inflammatory properties of BA.Results: The results showed that BA significantly reduced the mRNA levels of several pro-inflammatory cytokines induced by LPS both in BV-2 cells and iBMDMs. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in response to LPS were also decreased by BA. Further investigations indicated BA significantly blocked the phosphorylation of IκB kinase, degradation of the inhibitor IκBa and the nuclear translocation of nuclear factor-κB (NF-κB) p65. BA also reduced c-Jun N-terminal kinases (JNK) phosphorylation and ROS generation in iBMDMs activated with LPS, but had no effect on other mitogen-activated protein kinases (MAPKs) family proteins such as extracellular signal-regulated kinase (ERK) or p38. Furthermore, BA treatment alleviate liver and lung tissue damage, reduce inflammatory cell infiltration, and inhibit the expression of inflammatory cytokines in LPS-challenged mice.Conclusions: This study illustrated that BA has obvious anti-inflammatory effects both in vitro and in vivo, and its underlying anti-inflammatory mechanism may be via inactivating JNK/ROS/NF-κB pathway. Therefore, BA may have a certain therapeutic potential for inflammatory-related diseases.

Nanocurcumin: A Double-Edged Sword for Microcancers

2020 ◽  
Vol 26 (45) ◽  
pp. 5783-5792
Author(s):  
Kholood Abid Janjua ◽  
Adeeb Shehzad ◽  
Raheem Shahzad ◽  
Salman Ul Islam ◽  
Mazhar Ul Islam
Keyword(s):  
Intracellular Signaling ◽  
Dosage Forms ◽  
The Body ◽  
In Vivo Studies ◽  
Mrna Levels ◽  
Anticancer Activities ◽  
Road Map ◽  
Anticancer Effects

There is compelling evidence that drug molecules isolated from natural sources are hindered by low systemic bioavailability, poor absorption, and rapid elimination from the human body. Novel approaches are urgently needed that could enhance the retention time as well as the efficacy of natural products in the body. Among the various adopted approaches to meet this ever-increasing demand, nanoformulations show the most fascinating way of improving the bioavailability of dietary phytochemicals through modifying their pharmacokinetics and pharmacodynamics. Curcumin, a yellowish pigment isolated from dried ground rhizomes of turmeric, exhibits tremendous pharmacological effects, including anticancer activities. Several in vitro and in vivo studies have shown that curcumin mediates anticancer effects through the modulation (upregulation and/or downregulations) of several intracellular signaling pathways both at protein and mRNA levels. Scientists have introduced multiple modern techniques and novel dosage forms for enhancing the delivery, bioavailability, and efficacy of curcumin in the treatment of various malignancies. These novel dosage forms include nanoparticles, liposomes, micelles, phospholipids, and curcumin-encapsulated polymer nanoparticles. Nanocurcumin has shown improved anticancer effects compared to conventional curcumin formulations. This review discusses the underlying molecular mechanism of various nanoformulations of curcumin for the treatment of different cancers. We hope that this study will make a road map for preclinical and clinical investigations of cancer and recommend nano curcumin as a drug of choice for cancer therapy.

scholarly journals TRIM27 interacts with Iκbα to promote the growth of human renal cancer cells through regulating the NF-κB pathway

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chengwu Xiao ◽  
Wei Zhang ◽  
Meimian Hua ◽  
Huan Chen ◽  
Bin Yang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Abstract Background The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. Methods The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. Results We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. Conclusions Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.

Methylmercury-induced pro-inflammatory cytokines activation and its preventive strategy using anti-inflammation N-acetyl-l-cysteine: a mini-review

2020 ◽  
Vol 35 (3) ◽  
pp. 233-238
Author(s):  
Muflihatul Muniroh
Keyword(s):  
Inflammatory Cytokines ◽  
Health Concern ◽  
Brain Cells ◽  
Preventive Strategy ◽  
Hearing Impairments ◽  
Sensory Disturbances ◽  
Anti Inflammation ◽  
Pro Inflammatory Cytokines

AbstractThe exposure of methylmercury (MeHg) has become a public health concern because of its neurotoxic effect. Various neurological symptoms were detected in Minamata disease patients, who got intoxicated by MeHg, including paresthesia, ataxia, gait disturbance, sensory disturbances, tremors, visual, and hearing impairments, indicating that MeHg could pass the blood-brain barrier (BBB) and cause impairment of neurons and other brain cells. Previous studies have reported some expected mechanisms of MeHg-induced neurotoxicity including the neuroinflammation pathway. It was characterized by the up-regulation of numerous pro-inflammatory cytokines expression. Therefore, the use of anti-inflammatories such as N-acetyl-l-cysteine (NAC) may act as a preventive compound to protect the brain from MeHg harmful effects. This mini-review will explain detailed information on MeHg-induced pro-inflammatory cytokines activation as well as possible preventive strategies using anti-inflammation NAC to protect brain cells, particularly in in vivo and in vitro studies.

scholarly journals MBRS-48. IDENTIFICATION OF NOVEL THERAPEUTIC APPROACHES FOR MYC-DRIVEN MEDULLOBLASTOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii406-iii406
Author(s):  
Kübra Taban ◽  
David Pauck ◽  
Mara Maue ◽  
Viktoria Marquardt ◽  
Hua Yu ◽  
...  
Keyword(s):  
New Drugs ◽  
Current Therapy ◽  
Cancer Drug ◽  
Mrna Levels ◽  
Cell Models ◽  
Therapeutic Approaches ◽  
Group 3 ◽  
Novel Therapeutic

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children and is frequently metastatic at diagnosis. Treatment with surgery, radiation and multi-agent chemotherapy may leave survivors of these brain tumors with long-term deficits as a consequence. One of the four consensus molecular subgroups of MB is the MYC-driven group 3 MB, which is the most malignant type and has a poor prognosis under current therapy. Thus, it is important to discover more effective targeted therapeutic approaches. We conducted a high-throughput drug screening to identify novel compounds showing efficiency in group 3 MB using both clinically established inhibitors (n=196) and clinically-applicable compounds (n=464). More than 20 compounds demonstrated a significantly higher anti-tumoral effect in MYChigh (n=7) compared to MYClow (n=4) MB cell models. Among these compounds, Navitoclax and Clofarabine showed the strongest effect in inducing cell cycle arrest and apoptosis in MYChigh MB models. Furthermore, we show that Navitoclax, an orally bioavailable and blood-brain barrier passing anti-cancer drug, inhibits specifically Bcl-xL proteins. In line, we found a significant correlation between BCL-xL and MYC mRNA levels in 763 primary MB patient samples (Data source: “R2 https://hgserver1.amc.nl”). In addition, Navitoclax and Clofarabine have been tested in cells obtained from MB patient-derived-xenografts, which confirmed their specific efficacy in MYChigh versus MYClow MB. In summary, our approach has identified promising new drugs that significantly reduce cell viability in MYChigh compared to MYClow MB cell models. Our findings point to novel therapeutic vulnerabilities for MB that need to be further validated in vitro and in vivo.

scholarly journals N-palmitoyl-D-glucosamine, A Natural Monosaccharide-Based Glycolipid, Inhibits TLR4 and Prevents LPS-Induced Inflammation and Neuropathic Pain in Mice

2021 ◽  
Vol 22 (3) ◽  
pp. 1491 ◽  
Author(s):  
Monica Iannotta ◽  
Carmela Belardo ◽  
Maria Consiglia Trotta ◽  
Fabio Arturo Iannotti ◽  
Rosa Maria Vitale ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Inflammatory Cytokines ◽  
Lipid A ◽  
Saturated Fatty Acids ◽  
Structural Similarity ◽  
Antagonistic Activity ◽  
Critical Function ◽  
Anti Inflammatory

Toll-like receptors (TLRs) are key receptors through which infectious and non-infectious challenges act with consequent activation of the inflammatory cascade that plays a critical function in various acute and chronic diseases, behaving as amplification and chronicization factors of the inflammatory response. Previous studies have shown that synthetic analogues of lipid A based on glucosamine with few chains of unsaturated and saturated fatty acids, bind MD-2 and inhibit TLR4 receptors. These synthetic compounds showed antagonistic activity against TLR4 activation in vitro by LPS, but little or no activity in vivo. This study aimed to show the potential use of N-palmitoyl-D-glucosamine (PGA), a bacterial molecule with structural similarity to the lipid A component of LPS, which could be useful for preventing LPS-induced tissue damage or even peripheral neuropathies. Molecular docking and molecular dynamics simulations showed that PGA stably binds MD-2 with a MD-2/(PGA)3 stoichiometry. Treatment with PGA resulted in the following effects: (i) it prevented the NF-kB activation in LPS stimulated RAW264.7 cells; (ii) it decreased LPS-induced keratitis and corneal pro-inflammatory cytokines, whilst increasing anti-inflammatory cytokines; (iii) it normalized LPS-induced miR-20a-5p and miR-106a-5p upregulation and increased miR-27a-3p levels in the inflamed corneas; (iv) it decreased allodynia in peripheral neuropathy induced by oxaliplatin or formalin, but not following spared nerve injury of the sciatic nerve (SNI); (v) it prevented the formalin- or oxaliplatin-induced myelino-axonal degeneration of sciatic nerve. SIGNIFICANCE STATEMENT We report that PGA acts as a TLR4 antagonist and this may be the basis of its potent anti-inflammatory activity. Being unique because of its potency and stability, as compared to other similar congeners, PGA can represent a tool for the optimization of new TLR4 modulating drugs directed against the cytokine storm and the chronization of inflammation.

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