scholarly journals Production of Proinflammatory Cytokines and Chemokines During Neuroinflammation: Novel Roles for Estrogen Receptors α and β

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4916-4925 ◽  
Author(s):  
Candice M. Brown ◽  
Tara A. Mulcahey ◽  
Nicole C. Filipek ◽  
Phyllis M. Wise
Keyword(s):  
Estrogen Receptors ◽  
Proinflammatory Cytokines ◽  
Neurological Disorders ◽  
Chemokine Production ◽  
Neuroinflammatory Response ◽  
Cytokines And Chemokines ◽  
The Central Nervous System ◽  
Mice Brain ◽  
Estradiol 17Β

Neuroinflammation is a common feature of many neurological disorders, and it is often accompanied by the release of proinflammatory cytokines and chemokines. Estradiol-17β (E2) exhibits antiinflammatory properties, including the suppression of proinflammatory cytokines, in the central nervous system. However, the mechanisms employed by E2 and the role(s) of estrogen receptors (ERs) ERα and ERβ are unclear. To investigate these mechanisms, we employed an in vivo lipopolysaccharide (LPS) model of systemic inflammation in ovariectomized (OVX) and OVX and E2-treated (OVX+E2) mice. Brain levels of proinflammatory cytokines (IL-1β, IL-6, and IL-12p40) and chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL5/RANTES, and CXCL1/KC) were quantified in mice at 0 (sham), 3, 6, 12, and 24 h after infection using multiplex protein analysis. E2 treatment inhibited LPS-induced increases in all cytokines. In contrast, E2 treatment only suppressed CCL/RANTES chemokine concentrations. To determine whether ERα and ERβ regulate brain cytokine and chemokine levels, parallel experiments were conducted using ERα knockout and ERβ knockout mice. Our results revealed that both ERα and ERβ regulated proinflammatory cytokine and chemokine production through E2-dependent and E2-independent mechanisms. To assess whether breakdown of the blood-brain barrier is an additional target of E2 against LPS-induced neuroinflammation, we measured Evan’s blue extravasation and identified distinct roles for ERα and ERβ. Taken together, these studies identify a dramatic cytokine- and chemokine-mediated neuroinflammatory response that is regulated through ERα- and ERβ-mediated ligand-dependent and ligand-independent mechanisms.

scholarly journals Genetic Approaches Using Zebrafish to Study the Microbiota–Gut–Brain Axis in Neurological Disorders

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 566
Author(s):  
Jae-Geun Lee ◽  
Hyun-Ju Cho ◽  
Yun-Mi Jeong ◽  
Jeong-Soo Lee
Keyword(s):  
Neurological Disorders ◽  
Genetic Model ◽  
Molecular Genetic ◽  
Autism Spectrum ◽  
Behavioral Abnormalities ◽  
Bidirectional Signaling ◽  
Intestinal Dysbiosis ◽  
The Central Nervous System ◽  
The Brain

The microbiota–gut–brain axis (MGBA) is a bidirectional signaling pathway mediating the interaction of the microbiota, the intestine, and the central nervous system. While the MGBA plays a pivotal role in normal development and physiology of the nervous and gastrointestinal system of the host, its dysfunction has been strongly implicated in neurological disorders, where intestinal dysbiosis and derived metabolites cause barrier permeability defects and elicit local inflammation of the gastrointestinal tract, concomitant with increased pro-inflammatory cytokines, mobilization and infiltration of immune cells into the brain, and the dysregulated activation of the vagus nerve, culminating in neuroinflammation and neuronal dysfunction of the brain and behavioral abnormalities. In this topical review, we summarize recent findings in human and animal models regarding the roles of the MGBA in physiological and neuropathological conditions, and discuss the molecular, genetic, and neurobehavioral characteristics of zebrafish as an animal model to study the MGBA. The exploitation of zebrafish as an amenable genetic model combined with in vivo imaging capabilities and gnotobiotic approaches at the whole organism level may reveal novel mechanistic insights into microbiota–gut–brain interactions, especially in the context of neurological disorders such as autism spectrum disorder and Alzheimer’s disease.

scholarly journals Mycoplasma pneumoniae-Derived Lipopeptides Induce Acute Inflammatory Responses in the Lungs of Mice

2007 ◽  
Vol 76 (1) ◽  
pp. 270-277 ◽  
Author(s):  
Takashi Shimizu ◽  
Yutaka Kida ◽  
Koichi Kuwano
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Inflammatory Responses ◽  
Lavage Fluid ◽  
Peritoneal Macrophages ◽  
Necrosis Factor Alpha ◽  
Chemokine Production ◽  
Cytokines And Chemokines ◽  
Tnf Α ◽  
Mouse Peritoneal Macrophages

ABSTRACT The pathogenesis of Mycoplasma pneumoniae infection is considered to be in part attributable to excessive immune responses. In this study, we investigated whether synthetic lipopeptides of subunit b of F0F1-type ATPase (F0F1-ATPase), NF-κB-activating lipoprotein 1 (N-ALP1), and N-ALP2 (named FAM20, sN-ALP1, and sN-ALP2, respectively) derived from M. pneumoniae induce cytokine and chemokine production and leukocyte infiltration in vivo. Intranasal administration of FAM20 and sN-ALP2 induced infiltration of leukocyte cells and production of chemokines and cytokines in bronchoalveolar lavage fluid, but sN-ALP1 failed to do so. The activity of FAM20 was notably higher than that of sN-ALP2. FAM20 and sN-ALP2 induced tumor necrosis factor alpha (TNF-α) through Toll-like receptor 2 in mouse peritoneal macrophages. Moreover, in the range of low concentrations of lipopeptides, FAM20 showed relatively high activity of inducing TNF-α in mouse peritoneal macrophages compared to synthetic lipopeptides such as MALP-2 and FSL-1, derived from Mycoplasma fermentans and Mycoplasma salivarium, respectively. These findings indicate that the F0F1-ATPase might be a key molecule in inducing cytokines and chemokines contributing to inflammatory responses during M. pneumoniae infection in vivo.

scholarly journals Campylobacter jejuni-Induced Cytokine Responses in Avian Cells

2005 ◽  
Vol 73 (4) ◽  
pp. 2094-2100 ◽  
Author(s):  
Chris K. Smith ◽  
Pete Kaiser ◽  
Lisa Rothwell ◽  
Tom Humphrey ◽  
Paul A. Barrow ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Proinflammatory Cytokines ◽  
Disease Process ◽  
Avian Host ◽  
Macrophage Cell ◽  
Proinflammatory Response ◽  
Cytokines And Chemokines ◽  
Cytokine Responses ◽  
Chick Kidney

ABSTRACT Campylobacter jejuni is a major cause of human inflammatory enteritis. During the course of human disease numerous proinflammatory cytokines are produced. Little is known, however, about the cytokine responses produced during the interaction of this bacterium with the avian host. Campylobacter has been considered a commensal of the avian host. Any differences in innate responses to this pathogen between the human and avian hosts should lead to a greater understanding of the disease process in humans. We have demonstrated expression of proinflammatory cytokines and chemokines in response to Campylobacter infection in avian primary chick kidney cells and the avian macrophage cell line HD11. The data indicate that Campylobacter can stimulate the avian host in a proinflammatory manner. The data strongly suggest that the lack of pathology in vivo is not due to an inability of Campylobacter to stimulate a proinflammatory response from avian cells.

scholarly journals Is Saffron Able to Prevent the Dysregulation of Retinal Cytokines Induced by Ocular Hypertension in Mice?

2021 ◽  
Vol 10 (21) ◽  
pp. 4801
Author(s):  
José A. Fernández-Albarral ◽  
Miguel A. Martínez-López ◽  
Eva M. Marco ◽  
Rosa de Hoz ◽  
Beatriz Martín-Sánchez ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
Proinflammatory Cytokines ◽  
Control Group ◽  
Chemokine Production ◽  
Cytokines And Chemokines ◽  
Saffron Extract ◽  
Anti Inflammatory ◽  
Contralateral Eye ◽  
Laser Induction ◽  
Endothelial Growth Factor

Cytokine- and chemokine-mediated signalling is involved in the neuroinflammatory process that leads to retinal ganglion cell (RGC) damage in glaucoma. Substances with anti-inflammatory properties could decrease these cytokines and chemokines and thus prevent RGC death. The authors of this study analysed the anti-inflammatory effect of a hydrophilic saffron extract standardized to 3% crocin content, focusing on the regulation of cytokine and chemokine production, in a mouse model of unilateral laser-induced ocular hypertension (OHT). We demonstrated that following saffron treatment, most of the concentration of proinflammatory cytokines (IL-1β, IFN-γ, TNF-α, and IL-17), anti-inflammatory cytokines (IL-4 and IL-10), Brain-derived Neurotrophic Factor (BDNF), Vascular Endothelial Growth Factor (VEGF), and fractalkine were unaffected in response to laser-induced OHT in both the OHT eye and its contralateral eye. Only IL-6 levels were significantly increased in the OHT eye one day after laser induction compared with the control group. These results differed from those observed in animals subjected to unilateral OHT and not treated with saffron, where changes in cytokine levels occurred in both eyes. Therefore, saffron extract regulates the production of proinflammatory cytokines, VEGF, and fractalkine induced by increasing intraocular pressure (IOP), protecting the retina from inflammation. These results indicate that saffron could be beneficial in glaucoma by helping to reduce the inflammatory process.

scholarly journals Rotavirus Recombinant VP6 Nanotubes Act as an Immunomodulator and Delivery Vehicle for Norovirus Virus-Like Particles

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Maria Malm ◽  
Kirsi Tamminen ◽  
Suvi Lappalainen ◽  
Timo Vesikari ◽  
Vesna Blazevic
Keyword(s):  
Cell Surface ◽  
Cell Line ◽  
Surface Expression ◽  
Endocytic Pathway ◽  
Cell Surface Expression ◽  
Adjuvant Effect ◽  
Chemokine Production ◽  
Cytokines And Chemokines

We have recently shown that tubular form of rotavirus (RV) recombinant VP6 protein has anin vivoadjuvant effect on the immunogenicity of norovirus (NoV) virus-like particle (VLP) vaccine candidate. In here, we investigatedin vitroeffect of VP6 on antigen presenting cell (APC) activation and maturation and whether VP6 facilitates NoV VLP uptake by these APCs. Mouse macrophage cell line RAW 264.7 and dendritic cell line JAWSII were used as model APCs. Internalization of VP6, cell surface expression of CD40, CD80, CD86, and major histocompatibility class II molecules, and cytokine and chemokine production were analyzed. VP6 nanotubes were efficiently internalized by APCs. VP6 upregulated the expression of cell surface activation and maturation molecules and induced secretion of several proinflammatory cytokines and chemokines. The mechanism of VP6 action was shown to be partially dependent on lipid raft-mediated endocytic pathway as shown by methyl-β-cyclodextrin inhibition on tumor necrosis factorαsecretion. These findings add to the understanding of mechanism by which VP6 exerts its immunostimulatory and immunomodulatory actions and further support its use as a part of nonlive RV-NoV combination vaccine.

scholarly journals Cytokine and Chemokine Production by Human Oral and Vaginal Epithelial Cells in Response to Candida albicans

2002 ◽  
Vol 70 (2) ◽  
pp. 577-583 ◽  
Author(s):  
Chad Steele ◽  
Paul L. Fidel
Keyword(s):  
Candida Albicans ◽  
Epithelial Cells ◽  
Proinflammatory Cytokines ◽  
Transforming Growth Factor ◽  
Fungal Infections ◽  
Vaginal Mucosa ◽  
Local Immunity ◽  
Chemokine Production ◽  
Cytokines And Chemokines ◽  
Vaginal Epithelial Cells

ABSTRACT Oropharyngeal and vaginal candidiases are the most common forms of mucosal fungal infections and are primarily caused by Candida albicans, a dimorphic fungal commensal organism of the gastrointestinal and lower female reproductive tracts. Clinical and experimental observations suggest that local immunity is important in host defense against candidiasis. Accordingly, cytokines and chemokines are present at the oral and vaginal mucosa during C. albicans infections. Since mucosal epithelial cells produce a variety of cytokines and chemokines in response to microorganisms and since C. albicans is closely associated with mucosal epithelial cells as a commensal, we sought to identify cytokines and/or chemokines produced by primary oral and vaginal epithelial cells and cell lines in response to C. albicans. The results showed that proinflammatory cytokines were produced by oral and/or vaginal epithelial cells at various levels constitutively with considerable interleukin-1α (IL-1α) and tumor necrosis factor alpha, but not IL-6, produced in response to C. albicans. In contrast, Th1-type (IL-12 and gamma interferon) and Th2-type-immunoregulatory (IL-10 and transforming growth factor β) cytokines and the chemokines monocyte chemoattractant protein 1 and IL-8 were produced in low to undetectable concentrations with little additional production in response to C. albicans. Taken together, these results indicate that cytokines and chemokines are variably produced by oral and vaginal epithelial cells constitutively, as well as in response to C. albicans, and are predominated by proinflammatory cytokines.

Effects of P-gpMAbNano-structured material nanoparticles on epilepsy and expression of SRY-related HMG Box 21 in epilepsy

2020 ◽  
Vol 10 (4) ◽  
pp. 585-593
Author(s):  
Qi Li ◽  
Jing Deng ◽  
Juan Yang ◽  
Tao Xu ◽  
Xinyuan Yu ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Temporal Cortex ◽  
New Approach ◽  
Hmg Box ◽  
Transcription Inhibitors ◽  
The Central Nervous System ◽  
And Function ◽  
Necrosis Factor

SRY-related HMG box (SOX)21, one of the most highly expressed transcription inhibitors in the central nervous system (CNS), is involved in neurogenesis-related transcription and proliferation, which are associated with certain neurological disorders. However, it is the role of SOX21 in the pathogenesis of epilepsy remains unclear. In this study, our aim was to examine the expression and function of SOX21 in patients with temporal lobe epilepsy (TLE), as well as pentylenetetrazol (PTZ)-kindled rats, and to identify the possible roles of SOX21 in epileptogenesis. We found that SOX21 localized in neurons is upregulated, especially in TLE patients. SOX21 is present in the hippocampus or adjacent temporal cortex in the PTZ-kindled epileptic rat model. In addition, the P-gpMAbNano-structured material (PNM) nanoparticles carrying anti-epileptic drugs (AEDs) were injected into the epileptic model rats using an intravenous injection. The expression of tumor necrosis factor peptide in the rats was detected to verify whether the drug-carrying nanoparticles could bypass macrophages and reach the target for treatment. We also found an interaction between SOX21 and SOX2 in PTZ-kindled rats. These results indicate that SOX21 is mainly located in neurons and may regulate the pathogenesis of epilepsy, possibly in association with SOX2. Moreover, PNM nanoparticles equipped with AEDs can reach the target through macrophages in vivo, providing a new approach for the clinical treatment of epilepsy.

scholarly journals Crossing the blood-brain barrier with carbon dots: uptake mechanism and in vivo cargo delivery

2021 ◽  
Author(s):  
Elif S. Seven ◽  
Yasin B. Seven ◽  
Yiqun Zhou ◽  
Sijan Poudel-Sharma ◽  
Juan J. Diaz Rucco ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Neurological Disorders ◽  
Brain Barrier ◽  
Uptake Mechanism ◽  
Blood Brain ◽  
Cargo Delivery ◽  
The Central Nervous System

The blood-brain barrier (BBB) is a major obstacle for drug delivery to the central nervous system (CNS) such that most therapeutics lack efficacy against brain tumors or neurological disorders due...

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