scholarly journals Role of TLR4 in Neutrophil Dynamics and Functions: Contribution to Stroke Pathophysiology

2021 ◽  
Vol 12 ◽  
Author(s):  
Violeta Durán-Laforet ◽  
Carolina Peña-Martínez ◽  
Alicia García-Culebras ◽  
María Isabel Cuartero ◽  
Eng H. Lo ◽  
...  
Keyword(s):  
Inflammatory Process ◽  
Focal Cerebral Ischemia ◽  
Cell Types ◽  
Neutrophil Function ◽  
Specific Cell ◽  
Radical Oxygen Species ◽  
Physiological Conditions ◽  
Neuroprotective Strategies ◽  
Circadian Fluctuation

Background and PurposeThe immune response subsequent to an ischemic stroke is a crucial factor in its physiopathology and outcome. It is known that TLR4 is implicated in brain damage and inflammation after stroke and that TLR4 absence induces neutrophil reprogramming toward a protective phenotype in brain ischemia, but the mechanisms remain unknown. We therefore asked how the lack of TLR4 modifies neutrophil function and their contribution to the inflammatory process.MethodsIn order to assess the role of the neutrophilic TLR4 after stroke, mice that do not express TLR4 in myeloid cells (TLR4loxP/Lyz-cre) and its respective controls (TLR4loxP/loxP) were used. Focal cerebral ischemia was induced by occlusion of the middle cerebral artery and infarct size was measured by MRI. A combination of flow cytometry and confocal microscopy was used to assess different neutrophil characteristics (circadian fluctuation, cell surface markers, cell complexity) and functions (apoptosis, microglia engulfment, phagocytosis, NETosis, oxidative burst) in both genotypes.ResultsAs previously demonstrated, mice with TLR4 lacking-neutrophils had smaller infarct volumes than control mice. Our results show that the absence of TLR4 keeps neutrophils in a steady youth status that is dysregulated, at least in part, after an ischemic insult, preventing neutrophils from their normal circadian fluctuation. TLR4-lacking neutrophils showed a higher phagocytic activity in the basal state, they were preferentially engulfed by the microglia after stroke, and they produced less radical oxygen species (ROS) in the first stage of the inflammatory process.ConclusionsTLR4 is specifically involved in neutrophil dynamics under physiological conditions as well as in stroke-induced tissue damage. This research contributes to the idea that TLR4, especially when targeted in specific cell types, is a potential target for neuroprotective strategies.

scholarly journals Estrogen binding by leukocytes during phagocytosis,.

1977 ◽  
Vol 145 (4) ◽  
pp. 983-998 ◽  
Author(s):  
S J Klebanoff
Keyword(s):  
Chronic Granulomatous Disease ◽  
Reaction Mechanisms ◽  
Dehydrogenase Deficiency ◽  
Cell Types ◽  
Neutrophil Function ◽  
Granulomatous Disease ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Estrogen Binding ◽  
Two Populations

Estradiol binds covalently to normal leukocytes during phagocytosis. The binding involves three cell types, neutrophils, eosinophils, and monocytes and at least two reaction mechanisms, one involving the peroxidase of neutrophils and monocytes (myeloperoxidase [MPO]) and possibly the eosinophil peroxidase, and the second involving catalase. Binding is markedly reduced when leukocytes from patients with chronic granulomatous disease (CGD), severe leukocytic glucose 6-phosphate dehydrogenase deficiency, and familial lipochrome histiocytosis are employed and two populations of neutrophils, one which binds estradiol and one which does not, can be demonstrated in the blood of a CGD carrier. Leukocytes from patients with hereditary MPO deficiency also bind estradiol poorly although the defect is not as severe as in CGD. These findings are discussed in relation to the inactivation of estrogens during infection and the possible role of estrogens in neutrophil function.

scholarly journals Differential Pathways of Angiotensin II-Induced Extracellularly Regulated Kinase 1/2 Phosphorylation in Specific Cell Types: Role of Heparin-Binding Epidermal Growth Factor

2004 ◽  
Vol 18 (8) ◽  
pp. 2035-2048 ◽  
Author(s):  
Bukhtiar H. Shah ◽  
Akin Yesilkaya ◽  
J. Alberto Olivares-Reyes ◽  
Hung-Dar Chen ◽  
László Hunyady ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Types ◽  
Specific Cell ◽  
Heparin Binding ◽  
Epidermal Growth

scholarly journals CCL2: An Important Mediator Between Tumor Cells and Host Cells in Tumor Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiakang Jin ◽  
Jinti Lin ◽  
Ankai Xu ◽  
Jianan Lou ◽  
Chao Qian ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cell Types ◽  
Host Cells ◽  
Specific Cell ◽  
Tumor Patients ◽  
Multiple Tumor ◽  
Inflammatory Monocytes ◽  
Immunosuppressive Cell ◽  
Tumor Types

Tumor microenvironment (TME) formation is a major cause of immunosuppression. The TME consists of a considerable number of macrophages and stromal cells that have been identified in multiple tumor types. CCL2 is the strongest chemoattractant involved in macrophage recruitment and a powerful initiator of inflammation. Evidence indicates that CCL2 can attract other host cells in the TME and direct their differentiation in cooperation with other cytokines. Overall, CCL2 has an unfavorable effect on prognosis in tumor patients because of the accumulation of immunosuppressive cell subtypes. However, there is also evidence demonstrating that CCL2 enhances the anti-tumor capability of specific cell types such as inflammatory monocytes and neutrophils. The inflammation state of the tumor seems to have a bi-lateral role in tumor progression. Here, we review works focusing on the interactions between cancer cells and host cells, and on the biological role of CCL2 in these processes.

Role of Different Sponge Cell Types in Species Specific Cell Aggregation

1971 ◽  
Vol 230 (12) ◽  
pp. 126-128 ◽  
Author(s):  
H. A. JOHN ◽  
M. S. CAMPO ◽  
A. M. MACKENZIE ◽  
R. B. KEMP
Keyword(s):  
Cell Aggregation ◽  
Cell Types ◽  
Specific Cell ◽  
Sponge Cell ◽  
Species Specific

scholarly journals Genome-wide Analysis of Insomnia (N=1,331,010) Identifies Novel Loci and Functional Pathways

2018 ◽  
Author(s):  
Philip R. Jansen ◽  
Kyoko Watanabe ◽  
Sven Stringer ◽  
Nathan Skene ◽  
Julien Bryois ◽  
...  
Keyword(s):  
Animal Studies ◽  
Genetic Correlations ◽  
Cell Types ◽  
Reward Processing ◽  
Chromatin Interaction ◽  
Specific Cell ◽  
Metabolic Traits ◽  
Genome Wide ◽  
Insight Into

AbstractInsomnia is the second-most prevalent mental disorder, with no sufficient treatment available. Despite a substantial role of genetic factors, only a handful of genes have been implicated and insight into the associated neurobiological pathways remains limited. Here, we use an unprecedented large genetic association sample (N=1,331,010) to allow detection of a substantial number of genetic variants and gain insight into biological functions, cell types and tissues involved in insomnia complaints. We identify 202 genome-wide significant loci implicating 956 genes through positional, eQTL and chromatin interaction mapping. We show involvement of the axonal part of neurons, of specific cortical and subcortical tissues, and of two specific cell-types in insomnia: striatal medium spiny neurons and hypothalamic neurons. These cell-types have been implicated previously in the regulation of reward processing, sleep and arousal in animal studies, but have never been genetically linked to insomnia in humans. We found weak genetic correlations with other sleep-related traits, but strong genetic correlations with psychiatric and metabolic traits. Mendelian randomization identified causal effects of insomnia on specific psychiatric and metabolic traits. Our findings reveal key brain areas and cells implicated in the neurobiology of insomnia and its related disorders, and provide novel targets for treatment.

scholarly journals Rescue of Hepatic Phospholipid Remodeling Defect in iPLA2β-Null Mice Attenuates Obese but Not Non-Obese Fatty Liver

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1332
Author(s):  
Walee Chamulitrat ◽  
Chutima Jansakun ◽  
Huili Li ◽  
Gerhard Liebisch
Keyword(s):  
Fatty Liver ◽  
Cell Types ◽  
Specific Cell ◽  
Liver Inflammation ◽  
Alcoholic Fatty Liver ◽  
Calcium Independent Phospholipase A2 ◽  
Hydrolysis Of

Polymorphisms of group VIA calcium-independent phospholipase A2 (iPLA2β or PLA2G6) are positively associated with adiposity, blood lipids, and Type-2 diabetes. The ubiquitously expressed iPLA2β catalyzes the hydrolysis of phospholipids (PLs) to generate a fatty acid and a lysoPL. We studied the role of iPLA2β on PL metabolism in non-alcoholic fatty liver disease (NAFLD). By using global deletion iPLA2β-null mice, we investigated three NAFLD mouse models; genetic Ob/Ob and long-term high-fat-diet (HFD) feeding (representing obese NAFLD) as well as feeding with methionine- and choline-deficient (MCD) diet (representing non-obese NAFLD). A decrease of hepatic PLs containing monounsaturated- and polyunsaturated fatty acids and a decrease of the ratio between PLs and cholesterol esters were observed in all three NAFLD models. iPLA2β deficiency rescued these decreases in obese, but not in non-obese, NAFLD models. iPLA2β deficiency elicited protection against fatty liver and obesity in the order of Ob/Ob › HFD » MCD. Liver inflammation was not protected in HFD NAFLD, and that liver fibrosis was even exaggerated in non-obese MCD model. Thus, the rescue of hepatic PL remodeling defect observed in iPLA2β-null mice was critical for the protection against NAFLD and obesity. However, iPLA2β deletion in specific cell types such as macrophages may render liver inflammation and fibrosis, independent of steatosis protection.

scholarly journals Developmental regulation and tissue distribution of the liver transcription factor LFB1 (HNF1) in Xenopus laevis.

1993 ◽  
Vol 13 (1) ◽  
pp. 421-431 ◽  
Author(s):  
S Bartkowski ◽  
D Zapp ◽  
H Weber ◽  
G Eberle ◽  
C Zoidl ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Xenopus Laevis ◽  
Developmental Regulation ◽  
Cdna Probe ◽  
Cell Types ◽  
Specific Gene ◽  
Specific Cell ◽  
Early Appearance ◽  
Liver Cdna Library

The transcription factor LFB1 (HNF1) was initially identified as a regulator of liver-specific gene expression in mammals. It interacts with the promoter element HP1, which is functionally conserved between mammals and amphibians, suggesting that a homologous factor, XLFB1, also exists in Xenopus laevis. To study the role of LFB1 in early development, we isolated two groups of cDNAs coding for this factor from a Xenopus liver cDNA library by using a rat LFB1 cDNA probe. A comparison of the primary structures of the Xenopus and mammalian proteins shows that the myosin-like dimerization helix, the POU-A-related domain, the homeo-domain-related region, and the serine/threonine-rich activation domain are conserved between X. laevis and mammals, suggesting that all these features typical for LFB1 are essential for function. Using monoclonal antibodies, we demonstrate that XLFB1 is present not only in the liver but also in the stomach, intestine, colon, and kidney. In an analysis of the expression of XLFB1 in the developing Xenopus embryo, XLFB1 transcripts appear at the gastrula stage. The XLFB1 protein can be identified in regions of the embryo in which the liver diverticulum, stomach, gut, and pronephros are localized. The early appearance of XLFB1 expression during embryogenesis suggests that the tissue-specific transcription factor XLFB1 is involved in the determination and/or differentiation of specific cell types during organogenesis.

scholarly journals Cell-autonomous expression of the acid hydrolase galactocerebrosidase

2020 ◽  
Vol 117 (16) ◽  
pp. 9032-9041
Author(s):  
Christina R. Mikulka ◽  
Joshua T. Dearborn ◽  
Bruno A. Benitez ◽  
Amy Strickland ◽  
Lin Liu ◽  
...  
Keyword(s):  
Lysosomal Storage Diseases ◽  
Cell Types ◽  
Krabbe Disease ◽  
Specific Cell ◽  
Acid Hydrolase ◽  
Lysosomal Storage ◽  
Lysosomal Hydrolases ◽  
Soluble Acid ◽  
Enzyme Deficient

Lysosomal storage diseases (LSDs) are typically caused by a deficiency in a soluble acid hydrolase and are characterized by the accumulation of undegraded substrates in the lysosome. Determining the role of specific cell types in the pathogenesis of LSDs is a major challenge due to the secretion and subsequent uptake of lysosomal hydrolases by adjacent cells, often referred to as “cross-correction.” Here we create and validate a conditional mouse model for cell-autonomous expression of galactocerebrosidase (GALC), the lysosomal enzyme deficient in Krabbe disease. We show that lysosomal membrane-tethered GALC (GALCLAMP1) retains enzyme activity, is able to cleave galactosylsphingosine, and is unable to cross-correct. Ubiquitous expression of GALCLAMP1 fully rescues the phenotype of the GALC-deficient mouse (Twitcher), and widespread deletion of GALCLAMP1 recapitulates the Twitcher phenotype. We demonstrate the utility of this model by deleting GALCLAMP1 specifically in myelinating Schwann cells in order to characterize the peripheral neuropathy seen in Krabbe disease.

scholarly journals Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

2021 ◽  
Vol 22 (6) ◽  
pp. 2870
Author(s):  
Tsung-Chieh Lin ◽  
Michael Hsiao
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Leptin Receptor ◽  
Biological Effects ◽  
Prognostic Significance ◽  
Cell Types ◽  
Receptor Expression ◽  
Specific Cell ◽  
Signaling Axis

Leptin is an obesity-associated adipokine that is known to regulate energy metabolism and reproduction and to control appetite via the leptin receptor. Recent work has identified specific cell types other than adipocytes that harbor leptin and leptin receptor expression, particularly in cancers and tumor microenvironments, and characterized the role of this signaling axis in cancer progression. Furthermore, the prognostic significance of leptin in various types of cancer and the ability to noninvasively detect leptin levels in serum samples have attracted attention for potential clinical applications. Emerging findings have demonstrated the direct and indirect biological effects of leptin in regulating cancer proliferation, metastasis, angiogenesis and chemoresistance, warranting the exploration of the underlying molecular mechanisms to develop a novel therapeutic strategy. In this review article, we summarize and integrate transcriptome and clinical data from cancer patients together with the recent findings related to the leptin signaling axis in the aforementioned malignant phenotypes. In addition, a comprehensive analysis of leptin and leptin receptor distribution in a pancancer panel and in individual cell types of specific organs at the single-cell level is presented, identifying those sites that are prone to leptin-mediated tumorigenesis. Our results shed light on the role of leptin in cancer and provide guidance and potential directions for further research for scientists in this field.

scholarly journals Dynamic Role of Phospholipases A2 in Health and Diseases in the Central Nervous System

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2963
Author(s):  
Grace Y. Sun ◽  
Xue Geng ◽  
Tao Teng ◽  
Bo Yang ◽  
Michael K. Appenteng ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cellular Localization ◽  
Cell Types ◽  
Molecular Structures ◽  
Specific Cell ◽  
Phospholipases A2 ◽  
Cell Functions ◽  
The Central Nervous System

Phospholipids are major components in the lipid bilayer of cell membranes. These molecules are comprised of two acyl or alkyl groups and different phospho-base groups linked to the glycerol backbone. Over the years, substantial interest has focused on metabolism of phospholipids by phospholipases and the role of their metabolic products in mediating cell functions. The high levels of polyunsaturated fatty acids (PUFA) in the central nervous system (CNS) have led to studies centered on phospholipases A2 (PLA2s), enzymes responsible for cleaving the acyl groups at the sn-2 position of the phospholipids and resulting in production of PUFA and lysophospholipids. Among the many subtypes of PLA2s, studies have centered on three major types of PLA2s, namely, the calcium-dependent cytosolic cPLA2, the calcium-independent iPLA2 and the secretory sPLA2. These PLA2s are different in their molecular structures, cellular localization and, thus, production of lipid mediators with diverse functions. In the past, studies on specific role of PLA2 on cells in the CNS are limited, partly because of the complex cellular make-up of the nervous tissue. However, understanding of the molecular actions of these PLA2s have improved with recent advances in techniques for separation and isolation of specific cell types in the brain tissue as well as development of sensitive molecular tools for analyses of proteins and lipids. A major goal here is to summarize recent studies on the characteristics and dynamic roles of the three major types of PLA2s and their oxidative products towards brain health and neurological disorders.

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