scholarly journals 0177 Bovine macrophage phenotype influences inflammatory response to lipopolysaccharide

2016 ◽  
Vol 94 (suppl_5) ◽  
pp. 85-86
Author(s):  
W. Raphael ◽  
G. A. Contreras
Keyword(s):  
Inflammatory Response ◽  
Macrophage Phenotype ◽  
Bovine Macrophage

scholarly journals In vitro response of macrophages to ceramic scaffolds used for bone regeneration

2016 ◽  
Vol 13 (120) ◽  
pp. 20160346 ◽  
Author(s):  
Pamela L. Graney ◽  
Seyed-Iman Roohani-Esfahani ◽  
Hala Zreiqat ◽  
Kara L. Spiller
Keyword(s):  
Gene Expression ◽  
Inflammatory Response ◽  
Bone Regeneration ◽  
Bone Repair ◽  
Principal Component ◽  
Human Monocyte ◽  
Macrophage Phenotype ◽  
In Vitro Response

Macrophages, the primary cells of the inflammatory response, are major regulators of healing, and mediate both bone fracture healing and the inflammatory response to implanted biomaterials. However, their phenotypic contributions to biomaterial-mediated bone repair are incompletely understood. Therefore, we used gene expression and protein secretion analysis to investigate the interactions in vitro between primary human monocyte-derived macrophages and ceramic scaffolds that have been shown to have varying degrees of success in promoting bone regeneration in vivo . Specifically, baghdadite (Ca 3 ZrSi 2 O 9 ) and strontium–hardystonite–gahnite (Sr–Ca 2 ZnSi 2 O 7 –ZnAl 2 O 4 ) scaffolds were chosen as two materials that enhanced bone regeneration in vivo in large defects under load compared with clinically used tricalcium phosphate–hydroxyapatite (TCP–HA). Principal component analysis revealed that the scaffolds differentially regulated macrophage phenotype. Temporal changes in gene expression included shifts in markers of pro-inflammatory M1, anti-inflammatory M2a and pro-remodelling M2c macrophage phenotypes. Of note, TCP–HA scaffolds promoted upregulation of many M1-related genes and downregulation of many M2a- and M2c-related genes. Effects of the scaffolds on macrophages were attributed primarily to direct cell–scaffold interactions because of only minor changes observed in transwell culture. Ultimately, elucidating macrophage–biomaterial interactions will facilitate the design of immunomodulatory biomaterials for bone repair.

scholarly journals YAP/TAZ deficiency reprograms macrophage phenotype and improves infarct healing and cardiac function after myocardial infarction

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3000941
Author(s):  
Masum M. Mia ◽  
Dasan Mary Cibi ◽  
Siti Aishah Binte Abdul Ghani ◽  
Weihua Song ◽  
Nicole Tee ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Inflammatory Response ◽  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Macrophage Polarization ◽  
Myocardial Damage ◽  
Binding Motif ◽  
Hippo Signaling ◽  
Macrophage Phenotype ◽  
Functional Changes

Adverse cardiac remodeling after myocardial infarction (MI) causes structural and functional changes in the heart leading to heart failure. The initial post-MI pro-inflammatory response followed by reparative or anti-inflammatory response is essential for minimizing the myocardial damage, healing, and scar formation. Bone marrow–derived macrophages (BMDMs) are recruited to the injured myocardium and are essential for cardiac repair as they can adopt both pro-inflammatory or reparative phenotypes to modulate inflammatory and reparative responses, respectively. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the key mediators of the Hippo signaling pathway and are essential for cardiac regeneration and repair. However, their functions in macrophage polarization and post-MI inflammation, remodeling, and healing are not well established. Here, we demonstrate that expression of YAP and TAZ is increased in macrophages undergoing pro-inflammatory or reparative phenotype changes. Genetic deletion of YAP/TAZ leads to impaired pro-inflammatory and enhanced reparative response. Consistently, YAP activation enhanced pro-inflammatory and impaired reparative response. We show that YAP/TAZ promote pro-inflammatory response by increasing interleukin 6 (IL6) expression and impede reparative response by decreasing Arginase-I (Arg1) expression through interaction with the histone deacetylase 3 (HDAC3)-nuclear receptor corepressor 1 (NCoR1) repressor complex. These changes in macrophages polarization due to YAP/TAZ deletion results in reduced fibrosis, hypertrophy, and increased angiogenesis, leading to improved cardiac function after MI. Also, YAP activation augmented MI-induced cardiac fibrosis and remodeling. In summary, we identify YAP/TAZ as important regulators of macrophage-mediated pro-inflammatory or reparative responses post-MI.

ALDH1A1 Dysfunction in FA-Deficient Macrophages Contributes to Aberrant Activation of the Innate Immune Response

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4107-4107 ◽  
Author(s):  
Michael R Garbati ◽  
R. K. Rathbun ◽  
Jane E. Yates ◽  
Wenjin Yang ◽  
Grover C. Bagby
Keyword(s):  
Stem Cell ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Small Molecule ◽  
Conflicts Of Interest ◽  
Bone Marrow Failure ◽  
Macrophage Phenotype ◽  
Aldh Activity ◽  
Hematopoietic Stem ◽  
Normal Production

Abstract Recent work has clarified a role for aldehyde dehydrogenases in protecting Fanconi anemia (FA) hematopoietic stem cells (HSC) and indicates that the increase in endogenous aldehydes that attends the genetic loss of ALDH function is sufficient to induce bone marrow failure in this disease. Studies in many laboratories have also documented that: (1) exposure of FA HSC to inflammatory cytokines suppresses stem cell self-replication and, in vivo, exhausts the stem cell pool and (2) FA macrophages exposed to specific toll-like receptor (TLR) ligands overproduce the very inflammatory cytokines that suppress the HSC pool. Given that aldehydes form adducts with and, in some cases, activate signaling proteins involved in cytokine production, we tested the hypothesis that overproduction of inflammatory cytokines by FA macrophages results from a loss of FA protein-dependent ALDH function. We treated THP-1 human monocytic leukemia cells expressing shRNA targeting FANCC (T-shFC) or a non-targeted shRNA (T-shNT) with the aldehyde 4-hydroxynonenal (4-HNE) before exposing them to the TLR-7/8 agonist R848. 4-HNE alone did not induce TNF production in either cell line but did enhance TLR-induced TNF overproduction by T-shFC cells (but not T-shNT cells), suggesting that FANCC-deficient macrophages lack factors (e.g., ALDH) that neutralize a signal-enhancing effect of this aldehyde. To directly test the effects of ALDH loss, we pretreated cells with the general ALDH inhibitor diethylaminobenzaldehyde and found that this agent enhanced R848-induced normal production of TNF by approximately 1.6-fold in control cells but did not enhance TNF production in T-shFC cells that were already overproducing TNF. Having determined that ALDH1A1 (but not ALDH2) was highly inducible in both THP-1 cells (by R848) and Lin-Sca-1+Kit+ (by TNF) murine marrow cells, we used siRNA to suppress expression of ALDH2 or ALDH1A1. Knockdown of ALDH1A1 (but not ALDH2) enhanced R848-induced normal production of TNF by approximately 1.8-fold in T-shNT but not TNF overproduction in T-shFC (fig 1) or T-shFA (FANCA knockdown) cells. Our results are consistent with the notion that ALDH1A1 is non-functional in FANCC-deficient macrophages and we confirmed that suspicion in gain-of-function analyses. Specifically, treatment of T-shNT and T-shFC cells with Alda-1 (a small molecule ALDH agonist known to enhance the activity of both ALDH1A1 and ALDH2) suppressed TLR-induced TNF production (fig 2), even in the presence of 4-HNE, by both T-shNT and T-shFC cells. In summary, (1) increasing the aldehyde load in normal macrophages has little influences on the inflammatory response induced by TLR activation but in FANCC-deficient cells aldehydes exacerbate the inflammatory response, (2) suppression of ALDH function with DEAB and specific suppression of ALDH1A1, (but not ALDH2) induces an FA-like phenotype in control macrophages, and (3) pharmacological enhancement of ALDH activity suppresses induced cytokine overproduction by FANCC-deficient macrophages. We conclude that: (1) optimal function of ALDH1A1 is FANCC-dependent in normal macrophages, (2) that the TLR-dependent overproduction of inflammatory cytokines by FANCC-deficient macrophages may result either from an increase in the aldehyde load or the loss of a non-canonical signal-suppressive function of ALDH1A1, and (3) enhancement of ALDH activity using small molecule agonists such as Alda-1 may alleviate the FA macrophage phenotype and may thereby protect HSC from inflammation-induced exhaustion. Disclosures No relevant conflicts of interest to declare.

Macrophage phenotype during cholestatic injury and repair: The persistent inflammatory response

2001 ◽  
Vol 36 (1) ◽  
pp. 220-228 ◽  
Author(s):  
Kevin K. Roggin ◽  
Jenny C. Kim ◽  
Arlet G. Kurkchubasche ◽  
Elaine F. Papa ◽  
Alexander M. Vezeridis ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Macrophage Phenotype ◽  
Injury And Repair

scholarly journals Cortical bone stem cells modify cardiac inflammation after myocardial infarction by inducing a novel macrophage phenotype

2021 ◽  
Vol 321 (4) ◽  
pp. H684-H701
Author(s):  
Alexander R. H. Hobby ◽  
Remus M. Berretta ◽  
Deborah M. Eaton ◽  
Hajime Kubo ◽  
Eric Feldsott ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Inflammatory Response ◽  
Cell Therapy ◽  
Cortical Bone ◽  
Cardiac Injury ◽  
Macrophage Phenotype ◽  
Cardiac Inflammation

Cortical bone stem cell (CBSC) therapy after myocardial infarction alters the inflammatory response to cardiac injury. We found that cortical bone stem cell therapy induces a unique macrophage phenotype in vitro and can modulate macrophage/fibroblast cross talk.

scholarly journals Regulatory interactions between muscle and the immune system during muscle regeneration

2010 ◽  
Vol 298 (5) ◽  
pp. R1173-R1187 ◽  
Author(s):  
James G. Tidball ◽  
S. Armando Villalta
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Muscle Regeneration ◽  
Muscle Injury ◽  
Myeloid Cells ◽  
M2 Macrophages ◽  
Macrophage Phenotype ◽  
Dystrophic Muscle ◽  
M1 Macrophages ◽  
Th1 Response

Recent discoveries reveal complex interactions between skeletal muscle and the immune system that regulate muscle regeneration. In this review, we evaluate evidence that indicates that the response of myeloid cells to muscle injury promotes muscle regeneration and growth. Acute perturbations of muscle activate a sequence of interactions between muscle and inflammatory cells. The initial inflammatory response is a characteristic Th1 inflammatory response, first dominated by neutrophils and subsequently by CD68+M1 macrophages. M1 macrophages can propagate the Th1 response by releasing proinflammatory cytokines and cause further tissue damage through the release of nitric oxide. Myeloid cells in the early Th1 response stimulate the proliferative phase of myogenesis through mechanisms mediated by TNF-α and IL-6; experimental prolongation of their presence is associated with delayed transition to the early differentiation stage of myogenesis. Subsequent invasion by CD163+/CD206+M2 macrophages attenuates M1 populations through the release of anti-inflammatory cytokines, including IL-10. M2 macrophages play a major role in promoting growth and regeneration; their absence greatly slows muscle growth following injury or modified use and inhibits muscle differentiation and regeneration. Chronic muscle injury leads to profiles of macrophage invasion and function that differ from acute injuries. For example, mdx muscular dystrophy yields invasion of muscle by M1 macrophages, but their early invasion is accompanied by a subpopulation of M2a macrophages. M2a macrophages are IL-4 receptor+/CD206+cells that reduce cytotoxicity of M1 macrophages. Subsequent invasion of dystrophic muscle by M2c macrophages is associated with progression of the regenerative phase in pathophysiology. Together, these findings show that transitions in macrophage phenotype are an essential component of muscle regeneration in vivo following acute or chronic muscle damage.

The inflammatory response in pediatric biliary disease: Macrophage phenotype and distribution

1996 ◽  
Vol 31 (1) ◽  
pp. 121-126 ◽  
Author(s):  
Thomas F Tracy ◽  
Peter Dillon ◽  
Eben S Fox ◽  
Kathleen Minnick ◽  
Carole Vogler
Keyword(s):  
Inflammatory Response ◽  
Biliary Disease ◽  
Macrophage Phenotype

Gut permeabillity and nitric oxide: Evidence for an endotoxin mediated inflammatory response in severe acute pancreatitis

2001 ◽  
Vol 120 (5) ◽  
pp. A468-A469
Author(s):  
S RAHMAN ◽  
B AMMORI ◽  
I MARTIN ◽  
G BARCLAY ◽  
M LARVIN ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acute Pancreatitis ◽  
Inflammatory Response ◽  
Severe Acute Pancreatitis

ERK and PKCξ independently contribute to the EPEC-induced inflammatory response

2001 ◽  
Vol 120 (5) ◽  
pp. A126-A126
Author(s):  
S SAVKOVIC ◽  
Z KAPADIA ◽  
A KOUTSOURIS ◽  
G HECHT
Keyword(s):  
Inflammatory Response
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