Chemoattraction and Recruitment of Activated Immune Cells, Central Autonomic Control, and Blood Pressure Regulation

Elsaafien, Khalid; Korim, Willian S.; Setiadi, Anthony; May, Clive N.; Yao, Song T.

doi:10.3389/fphys.2019.00984

Cited by 13 publications

(12 citation statements)

References 71 publications

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“…Indeed, IL-6 administration in rat neurons led to an increase in p-tau species but not total tau, through activation of JAK/STAT and MAPK-p38 (60). IL-6 and CCL2 can induce each other and cooperatively elicit chemoattraction and recruitment of activated immune cells in a positive feedback loop to maintain and amplify a proinflammatory-like profile (61)(62)(63). Further analysis would be necessary to consider whether a similar pathway was involved in the worsening of tau pathology observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

CCL2 Overexpression in the Brain Promotes Glial Activation and Accelerates Tau Pathology in a Mouse Model of Tauopathy

et al. 2020

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Innate immune activation is a major contributor to Alzheimer's Disease (AD) pathophysiology, although the mechanisms involved are poorly understood. Chemokine C-C motif ligand (CCL) 2 is produced by neurons and glial cells and is upregulated in the AD brain. Transgene expression of CCL2 in mouse models of amyloidosis produces microglia-induced amyloid β oligomerization, a strong indication of the role of these activation pathways in the amyloidogenic processes of AD. We have previously shown that CCL2 polarizes microglia in wild type mice. However, how CCL2 signaling contributes to tau pathogenesis remains unknown. To address this question, CCL2 was delivered via recombinant adeno-associated virus serotype 9 into both cortex and hippocampus of a mouse model with tau pathology (rTg4510). We report that CCL2 overexpression aggravated tau pathology in rTg4510 as shown by the increase in Gallyas stained neurofibrillary tangles as well as phosphorylated tau-positive inclusions. In addition, biochemical analysis showed a reduction in the levels of detergent-soluble tau species followed by increase in the insoluble fraction, indicating a shift toward larger tau aggregates. Indeed, increased levels of high molecular weight species of phosphorylated tau were found in the mice injected with CCL2. We also report that worsening of tau pathology following CCL2 overexpression was accompanied by a distinct inflammatory response. We report an increase in leukocyte common antigen (CD45) and Cluster of differentiation 68 (CD68) expression in the brain of rTg4510 mice without altering the expression levels of a cell-surface protein Transmembrane Protein 119 (Tmem119) and ionized calcium-binding adaptor molecule 1 (Iba-1) in resident microglia. Furthermore, the analysis of cytokines in brain extract showed a significant increase in interleukin (IL)-6 and CCL3, while CCL5 levels were decreased in CCL2 mice. No changes were observed in IL-1α, IL-1β, TNF-α. IL-4, Vascular endothelial growth factor-VEGF, IL-13 and CCL11.Joly-Amado et al. CCL2 and Tau PathologyTaken together our data report for the first time that overexpression of CCL2 promotes the increase of pathogenic tau species and is associated with glial neuroinflammatory changes that are deleterious. We propose that these events may contribute to the pathogenesis of Alzheimer's disease and other tauopathies.

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Section: Discussionmentioning

confidence: 99%

CCL2 Overexpression in the Brain Promotes Glial Activation and Accelerates Tau Pathology in a Mouse Model of Tauopathy

et al. 2020

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“…growth factors, oxidative stress or other pro-inflammatory cytokines. CCL2 recruits circulating monocytes and macrophages to the site of injury or inflamed tissue [ 54 ]. The chemokines CXCL9 and CXCL10, secreted upon exposure to zymosan or yeast-b and zymosan, respectively, are produced by monocytes, macrophages and cancer cells in response to IFN-y [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Curdlan, zymosan and a yeast-derived β-glucan reshape tumor-associated macrophages into producers of inflammatory chemo-attractants

Graaff

Berrevoets

Rösch

et al. 2020

Cancer Immunol Immunother

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Anti-cancer T-cell responses are often halted due to the immune-suppressive micro-environment, in part related to tumorassociated macrophages. In the current study, we assessed indigestible β-glucans (oatβG, curdlan, grifolan, schizophyllan, lentinan, yeast whole glucan particles (yWGP), zymosan and two additional yeast-derived β-glucans a and b) for their physicochemical properties as well as their effects on the plasticity of human monocyte-derived macrophages that were polarized with IL-4 to immune-suppressive macrophages. Beta-glucans were LPS/LTA free, and tested for solubility, molecular masses, protein and monosaccharide contents. Curdlan, yeast-b and zymosan re-polarized M(IL-4) macrophages towards an M1-like phenotype, in particular showing enhanced gene expression of CCR7, ICAM1 and CD80, and secretion of TNF-α and IL-6. Notably, differential gene expression, pathway analysis as well as protein expressions demonstrated that M(IL-4) macrophages treated with curdlan, yeast-b or zymosan demonstrated enhanced production of chemo-attractants, such as CCL3, CCL4, and CXCL8, which contribute to recruitment of monocytes and neutrophils. The secretion of chemo-attractants was confirmed when using patient-derived melanoma-infiltrating immune cells. Taken together, the bacterial-derived curdlan as well as the yeast-derived β-glucans yeast-b and zymosan have the unique ability to preferentially skew macrophages towards a chemoattractant-producing phenotype that may aid in anti-cancer immune responses. Keywords Beta-glucans • Macrophages • Chemokines • Chemo-attractants Abbreviations CR3 Complement receptor 3 Conv CD4 T cell Conventional cluster of differentiation 4 T cell LacCer Lactosylceramide LCF Lymphocyte chemoattractant factor LTA Lipoteichoic acid Tig-2 Tazarotene-induced gene 2 protein Treg Regulatory T cell yWGP Yeast whole glucan particle

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“…We previously found in SIH rats that Th17 cells invaded PVN and released IL-17, which induced elevation of blood pressure when injected to PVN [ 6 ]. The adaptive immune cells in distinct brain regions were recruited by chemokines [ 14 ]. To assess the contribution of chemokines to neuroinflammation in PVN of SIH rats, we performed cytokine antibody array assay for PVN tissues.…”

Section: Discussionmentioning

confidence: 99%

“…In SIH rats, the activated microglia in PVN mainly produce proinflammatory cytokines that promote inflammation and SIH [ 7 ]. In addition to resident microglia, the peripheral immune cells infiltrating into the brain are also involved in neuroinflammation and the development of hypertension [ 14 ]. Moreover, we have proven that the permeability of the blood-brain barrier in SIH rats increased and Th17 cells invaded the parenchyma of PVN to secrete IL-17, which facilitated neuroinflammation and the development of hypertension [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Upregulation of Chemokines in the Paraventricular Nucleus of the Hypothalamus in Rats with Stress-Induced Hypertension

Chen

Zhang

et al. 2020

Med Sci Monit

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Background The neuroinflammation of paraventricular nucleus (PVN) of the hypothalamus has been implicated in the development of hypertension. The promoted invasion of peripheral immune cells into PVN may be attributed to the upregulation of chemokines, then exacerbating neuroinflammation. We studied the expressions of chemokines, activation of microglial cells, and inflammatory mediators in PVN of rats with stress-induced hypertension (SIH). Material/Methods SIH was induced by electrical foot shock combined with noise for 2 h twice a day, at an interval of 4 h for 14 consecutive days. At the end of the 14th day, fresh PVN tissues were collected to measure the expressions of chemokines using the RayBiotech antibody array. Results We are the first to report that the expression of CXCL7 was extremely high in PVN of control rats, and was significantly lower in SIH rats. The expressions of CCL2 and CX3CL1 in PVN of SIH rats significantly exceeded those of control rats. The numbers of CX3CR1 (receptor of CX3CL1)-immunostained cells and oxycocin-42 (OX-42, marker of microglia)-positive cells increased in PVN of the SIH rats. The stress enhanced the protein expressions of proinflammatory cytokines IL-6 and IL-17 and reduced those of anti-inflammatory cytokines TGF-β and IL-10 in PVN. Conclusions In PVN of SIH rats, chronic stress induced neuroinflammation characterized by the activated microglia and upregulated proinflammatory cytokines. Expressions of chemokines CXCL7, CX3CL1, and CCL2 were altered. The causal link of chemokines to PVN neuroinflammation and hypertension remain to be determined.

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Chemoattraction and Recruitment of Activated Immune Cells, Central Autonomic Control, and Blood Pressure Regulation

Cited by 13 publications

References 71 publications

CCL2 Overexpression in the Brain Promotes Glial Activation and Accelerates Tau Pathology in a Mouse Model of Tauopathy

CCL2 Overexpression in the Brain Promotes Glial Activation and Accelerates Tau Pathology in a Mouse Model of Tauopathy

Curdlan, zymosan and a yeast-derived β-glucan reshape tumor-associated macrophages into producers of inflammatory chemo-attractants

Upregulation of Chemokines in the Paraventricular Nucleus of the Hypothalamus in Rats with Stress-Induced Hypertension

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