The GLP-1 receptor agonist Liraglutide attenuates intermittent hypoxia-induced pro-inflammatory macrophage polarization in primary macrophages

2021 ◽  
Author(s):  
Ailbhe King ◽  
Susan Fitzpatrick ◽  
Cliona O'Donnell ◽  
Silke Ryan
Keyword(s):  
Intermittent Hypoxia ◽  
Receptor Agonist ◽  
Macrophage Polarization ◽  
Inflammatory Macrophage

An in vitro test system for compounds that modulate human inflammatory macrophage polarization

2018 ◽  
Vol 833 ◽  
pp. 328-338 ◽  
Author(s):  
Hiromi Shiratori ◽  
Carmen Feinweber ◽  
Sonja Luckhardt ◽  
Nadja Wallner ◽  
Gerd Geisslinger ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Test System ◽  
In Vitro Test ◽  
Vitro Test ◽  
Inflammatory Macrophage

scholarly journals Macrophage-associated pro-inflammatory state in human islets from obese individuals

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Wei He ◽  
Ting Yuan ◽  
Kathrin Maedler
Keyword(s):  
Inflammatory Cytokines ◽  
Macrophage Polarization ◽  
Human Islets ◽  
Macrophage Phenotype ◽  
Inflammatory State ◽  
Obese Control ◽  
Inflammatory Macrophages ◽  
Inflammatory Macrophage ◽  
Pro Inflammatory Cytokines

AbstractObesity is associated with inflammatory macrophages in insulin responsive tissues and the resulting inflammatory response is a major contributor to insulin resistance. In insulin-producing pancreatic islets, the intra-islet accumulation of macrophages is observed in patients of type 2 diabetes (T2D), but such has not been investigated in obese individuals. Here, we show that pro-inflammatory cytokines (IL-1β, IL-6, and TNF), anti-inflammatory cytokines (IL-10 and TGF-β) and macrophage polarization markers (CD11c, CD163, and NOS2) were expressed in isolated human islets from non-diabetic donors. Clodronate-mediated depletion of resident macrophages revealed expression of IL1B and IL10 mostly from macrophages, while IL6, TNF, and TGFB1 came largely from a non-macrophage origin in human islets. NOS2 expression came exclusively from non-macrophage cells in non-obese individuals, while it originated also from macrophages in obese donors. Macrophage marker expression of CD68, CD163, and ITGAX was unchanged in islets of non-obese control and obese cohorts. In contrast, IL1B and NOS2 were significantly increased in islets from obese, compared to non-obese individuals, implying a more inflammatory macrophage phenotype in islets in obesity. Our study shows elevated macrophage-associated inflammation in human islets in obesity, which could be an initiating factor to the pro-inflammatory intra-islet milieu and contribute to the higher susceptibility to T2D in obese individuals.

scholarly journals Salmonella persisters undermine host immune defenses during antibiotic treatment

Science ◽  
2018 ◽  
Vol 362 (6419) ◽  
pp. 1156-1160 ◽  
Author(s):  
Daphne A. C. Stapels ◽  
Peter W. S. Hill ◽  
Alexander J. Westermann ◽  
Robert A. Fisher ◽  
Teresa L. Thurston ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Macrophage Polarization ◽  
Physiological State ◽  
Innate Immune Responses ◽  
Macrophage Infection ◽  
Immune Defenses ◽  
Type 3 Secretion System ◽  
Type 3 ◽  
Inflammatory Macrophage

Many bacterial infections are hard to treat and tend to relapse, possibly due to the presence of antibiotic-tolerant persisters. In vitro, persister cells appear to be dormant. After uptake of Salmonella species by macrophages, nongrowing persisters also occur, but their physiological state is poorly understood. In this work, we show that Salmonella persisters arising during macrophage infection maintain a metabolically active state. Persisters reprogram macrophages by means of effectors secreted by the Salmonella pathogenicity island 2 type 3 secretion system. These effectors dampened proinflammatory innate immune responses and induced anti-inflammatory macrophage polarization. Such reprogramming allowed nongrowing Salmonella cells to survive for extended periods in their host. Persisters undermining host immune defenses might confer an advantage to the pathogen during relapse once antibiotic pressure is relieved.

scholarly journals Adrenergic α1 receptor activation is sufficient, but not necessary for phrenic long-term facilitation

2014 ◽  
Vol 116 (11) ◽  
pp. 1345-1352 ◽  
Author(s):  
A. G. Huxtable ◽  
P. M. MacFarlane ◽  
S. Vinit ◽  
N. L. Nichols ◽  
E. A. Dale ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Intermittent Hypoxia ◽  
Receptor Agonist ◽  
Receptor Activation ◽  
Motor Nucleus ◽  
Long Term Facilitation ◽  
Dose Dependent

Acute intermittent hypoxia (AIH; three 5-min hypoxic episodes) causes a form of phrenic motor facilitation (pMF) known as phrenic long-term facilitation (pLTF); pLTF is initiated by spinal activation of Gq protein-coupled 5-HT2 receptors. Because α1 adrenergic receptors are expressed in the phrenic motor nucleus and are also Gq protein-coupled, we hypothesized that α1 receptors are sufficient, but not necessary for AIH-induced pLTF. In anesthetized, paralyzed, and ventilated rats, episodic spinal application of the α1 receptor agonist phenylephrine (PE) elicited dose-dependent pMF (10 and 100 μM, P < 0.05; but not 1 μM). PE-induced pMF was blocked by the α1 receptor antagonist prazosin (1 mM; −20 ± 20% at 60 min, −5 ± 21% at 90 min; n = 6). Although α1 receptor activation is sufficient to induce pMF, it was not necessary for AIH-induced pLTF because intrathecal prazosin (1 mM) did not alter AIH-induced pLTF (56 ± 9% at 60 min, 78 ± 12% at 90 min; n = 9). Intravenous (iv) prazosin (150 μg/kg) appeared to reduce pLTF (21 ± 9% at 60 min, 26 ± 8% at 90 min), but this effect was not significant. Hypoglossal long-term facilitation was unaffected by intrathecal prazosin, but was blocked by iv prazosin (−4 ± 14% at 60 min, −13 ± 18% at 90 min), suggesting different LTF mechanisms in different motor neuron pools. In conclusion, Gq protein-coupled α1 adrenergic receptors evoke pMF, but they are not necessary for AIH-induced pLTF.

scholarly journals RIG-I-like receptors direct inflammatory macrophage polarization against West Nile virus infection

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Amy E. L. Stone ◽  
Richard Green ◽  
Courtney Wilkins ◽  
Emily A. Hemann ◽  
Michael Gale
Keyword(s):  
West Nile Virus ◽  
Virus Infection ◽  
Macrophage Polarization ◽  
West Nile Virus Infection ◽  
West Nile ◽  
Inflammatory Macrophage

scholarly journals The Effect of miR-146a on the Gene Expression of Immunoregulatory Cytokines in Human Mesenchymal Stromal Cells

2020 ◽  
Vol 21 (18) ◽  
pp. 6809
Author(s):  
Jung Hwa Ko ◽  
Joo Youn Oh
Keyword(s):  
Stromal Cells ◽  
Macrophage Activation ◽  
Macrophage Polarization ◽  
Activated Macrophages ◽  
Mirna Microarray ◽  
Immunoregulatory Cytokines ◽  
Hepatocyte Growth ◽  
Inflammatory Macrophage ◽  
Necrosis Factor ◽  
Inducible Gene

Mounting evidence indicates that microRNAs (miRNAs), including miR-146a, have an impact on the immunomodulatory activities of mesenchymal stem/stromal cells (MSCs). Suppression of inflammatory macrophage activation is one of the main immunomodulatory mechanisms of MSCs. Here, we investigated whether miR-146a in MSCs might play a role in the effects of MSCs on macrophage activation. A miRNA microarray revealed that miR-146a was the most highly upregulated miRNA in MSCs upon co-culture with activated macrophages. Inhibition of miR-146a in MSCs through miR-146a inhibitor transfection had a different effect on the expression of immunoregulatory factors secreted by MSCs. Pentraxin 3, tumor necrosis factor-inducible gene 6, and cyclooxygenase-2, which are well-known mediators of the immunomodulatory functions of MSCs, were significantly upregulated in MSCs after miR-146a knockdown. By contrast, hepatocyte growth factor and stanniocalcin 1, other immunoregulatory molecules expressed by MSCs, were downregulated by miR-146a knockdown. Consequently, the inhibition of miR-146a in MSCs did not change the overall effect of MSCs on the suppression of inflammatory macrophage activation or the induction of anti-inflammatory macrophage polarization.

Transcriptional Characteristics of Activated Macrophages

2019 ◽  
Vol 25 (3) ◽  
pp. 213-217 ◽  
Author(s):  
Victor Glanz ◽  
Veronika A. Myasoedova ◽  
Vasily Sukhorukov ◽  
Andrey Grechko ◽  
Dongwei Zhang ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Macrophage Polarization ◽  
Integrated Approach ◽  
Future Research ◽  
The Novel ◽  
Activated Macrophages ◽  
Cell Debris ◽  
Exact Role ◽  
Inflammation Resolution ◽  
Inflammatory Macrophage

Macrophages are key players in human innate immunity that protect the organism from pathologic agents, including infection and malignant cells. The spectrum of their functions includes initiation and maintaining of inflammation, cleaning of pathogens and cell debris, as well as inflammation resolution and tissue remodeling and repair. Such a wide spectrum is reflected by the great variety of macrophage phenotypes based on the activation of distinct transcription patterns in response to different stimuli. Studying this complexity requires an integrated approach, such as transcriptome studies. For many genes, the exact role in macrophage biology remains unknown, although clear associations with pro- or anti-inflammatory macrophage polarization could be demonstrated. These findings reveal the novel directions for future research. In this review, we describe the known mechanisms of macrophage polarization and the new insights available from transcriptome studies.

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