scholarly journals Resveratrol Counteracts Inflammation in Human M1 and M2 Macrophages upon Challenge with 7-Oxo-Cholesterol: Potential Therapeutic Implications in Atherosclerosis

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Brigitta Buttari ◽  
Elisabetta Profumo ◽  
Luca Segoni ◽  
Daniela D’Arcangelo ◽  
Stefania Rossi ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Gelatin Zymography ◽  
Human Monocyte ◽  
M2 Macrophages ◽  
Potential Mechanism ◽  
Polyphenolic Compound ◽  
Autoxidation Product ◽  
Multiplex Immunoassay ◽  
Therapeutic Implications ◽  
M1 And M2 Macrophages

Macrophages consist of two main subsets: the proinflammatory M1 subset and the anti-inflammatory M2 one. 7-oxo-cholesterol, the most abundant cholesterol autoxidation product within atherosclerotic plaque, is able to skew the M1/M2 balance towards a proinflammatory profile. In the present study, we explored the ability of the polyphenolic compound resveratrol to counteract the 7-oxo-cholesterol-triggered proinflammatory signaling in macrophages. Resveratrol-pretreated human monocyte-derived M1 and M2 macrophages were challenged with 7-oxo-cholesterol and analyzed for phenotype and endocytic ability by flow cytometry, for metalloproteinase- (MMP-) 2 and MMP-9 by gelatin zymography, and for cytokine, chemokine, and growth factor secretome by a multiplex immunoassay. We also investigated the NF-κB signaling pathway. In the M1 subset, resveratrol prevented the downregulation of CD16 and the upregulation of MMP-2 in response to 7-oxo-cholesterol, whereas in M2 macrophages it prevented the upregulation of CD14, MMP-2, and MMP-9 and the downregulation of endocytosis. Resveratrol prevented the upregulation of several proinflammatory and proangiogenic molecules in both subsets. We identified modulation of NF-κB as a potential mechanism implicated in 7-oxo-cholesterol and resveratrol effects. Our results strengthen previous findings on the immunomodulatory ability of resveratrol and highlight its role as potential therapeutic or preventive compound, to counteract the proatherogenic oxysterol signaling within atherosclerotic plaque.

High glucose induces donors-specific cytokine response in primary human M1 and M2 macrophages

2015 ◽  
Vol 10 (S 01) ◽  
Author(s):  
K Moganti ◽  
F Li ◽  
S Riehman ◽  
H Klüter ◽  
M Harmsen ◽  
...  
Keyword(s):  
High Glucose ◽  
Cytokine Response ◽  
M2 Macrophages ◽  
M1 And M2 Macrophages

scholarly journals VitA or VitD ameliorates bronchopulmonary dysplasia by regulating the balance between M1 and M2 macrophages

2021 ◽  
Vol 141 ◽  
pp. 111836
Author(s):  
Hong Zhen ◽  
Hongbo Hu ◽  
Guojie Rong ◽  
Xiuxiu Huang ◽  
Chang Tan ◽  
...  
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
M2 Macrophages ◽  
M1 And M2 Macrophages

M1 and M2 Macrophages: Oracles of Health and Disease

2012 ◽  
Vol 32 (6) ◽  
pp. 463-488 ◽  
Author(s):  
Charles Mills
Keyword(s):  
M2 Macrophages ◽  
Health And Disease ◽  
M1 And M2 Macrophages

scholarly journals Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Tetsuya Kimura ◽  
Shigeyuki Nada ◽  
Noriko Takegahara ◽  
Tatsusada Okuno ◽  
Satoshi Nojima ◽  
...  
Keyword(s):  
Amino Acid ◽  
Macrophage Activation ◽  
Adaptor Protein ◽  
M2 Macrophages ◽  
Downstream Target ◽  
Mechanistic Target Of Rapamycin ◽  
M2 Polarization ◽  
M1 Polarization ◽  
Amino Acid Sensing ◽  
M1 And M2 Macrophages

Abstract Macrophages play crucial roles in host defence and tissue homoeostasis, processes in which both environmental stimuli and intracellularly generated metabolites influence activation of macrophages. Activated macrophages are classified into M1 and M2 macrophages. It remains unclear how intracellular nutrition sufficiency, especially for amino acid, influences on macrophage activation. Here we show that a lysosomal adaptor protein Lamtor1, which forms an amino-acid sensing complex with lysosomal vacuolar-type H+-ATPase (v-ATPase), and is the scaffold for amino acid-activated mTORC1 (mechanistic target of rapamycin complex 1), is critically required for M2 polarization. Lamtor1 deficiency, amino-acid starvation, or inhibition of v-ATPase and mTOR result in defective M2 polarization and enhanced M1 polarization. Furthermore, we identified liver X receptor (LXR) as the downstream target of Lamtor1 and mTORC1. Production of 25-hydroxycholesterol is dependent on Lamtor1 and mTORC1. Our findings demonstrate that Lamtor1 plays an essential role in M2 polarization, coupling immunity and metabolism.

Increased Alternative Macrophage-2 (M2) Polarization with Trib1 Gene over Expression in Myeloma Patients with Progressive Disease and Jak2 Inhibitors Reduce M2 Polarization

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1011-1011 ◽  
Author(s):  
Haiming Chen ◽  
Mingjie Li ◽  
Eric Sanchez ◽  
Abigail Gillespie ◽  
Cathy Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Progressive Disease ◽  
Scid Mice ◽  
Human Monocytes ◽  
M2 Macrophages ◽  
Jak2 Inhibitor ◽  
M2 Polarization ◽  
M1 And M2 Macrophages

Abstract Introduction: The bone marrow (BM) microenvironment plays an important role in multiple myeloma (MM). The BM niche is composed of multiple cell types including macrophages. Macrophages polarize into pro-inflammatory macrophage-1 (M1) or alternative M2 states that promote tumor growth and metastasis. We evaluated the proportion of M2 macrophages in BM from MM pts either showing complete response (CR) or progressive disease (PD), the effects of MM cells on M1 and M2 differentiation, and the role of Trib1 in M2 differentiation in MM BM. Since the JAK-STAT signaling pathway plays key roles in macrophages, we also evaluated the effects of the JAK2 inhibitor ruxolitinib (RUX) on M2 polarization in MM. Methods: Using immunofluorescence (IFC), we determined the proportion of M1 and M2 macrophages in BM biopsies and aspirates from MM pts with PD or CR. The BM biopsy samples were stained with antibodies directed against human iNOS and CD86 for M1 and arginase 1(ARG1) and CD36 for M2 cells. MM BM aspirates were also examined using flow cytometric analysis (FCA). Human monocytes isolated from healthy subjects or the THP1 monocyte cell line were co-cultured with MM cell lines (RPMI8226 and U266) or primary MM tumor cells. The effects of RUX at low concentrations (IC20) on M2 polarization were determined. The percentages of M1 and M2 macrophages were determined using FCA. Total RNA was extracted from monocytes. Quantitative PCR was measured with TaqMan technology. For the in vivo studies, human MM tumors (LAGκ-2) were surgically implanted into the left superficial gluteal muscle of SCID mice and tumor volume measured on a weekly basis. Results: The proportion of M2 macrophages (CD36+/ARG1+) was markedly increased in BM biopsies or mononuclear cells from MM pts with PD compared with those in CR using IFC staining. FCA also showed the percentage of M2 macrophages in BM was significantly increased in MM pts with PD (n=25) compared to those in CR (n=10; P=0.005) whereas there was no difference in the percentage of M1 (CD86+/iNOS+) macrophages in BM derived from MM pts with PD compared to those in CR. Trib1 gene mRNA levels were higher among pts with PD compared to those in CR whereas the gene expression of Trib2 and Trib3 was not different. Next, we co-cultured MM cell lines (U266) or fresh MM BMMCs with purified healthy human monocytes for one week. The percentage of M2 cells markedly increased and the proportion of M1 cells decreased. Trib1 gene expression increased during co-culture whereas there was no change in expression of the other two Tribs. When direct cell-to-cell contact occurred between the MM tumor cells and the monocytes, the percentage of M2 macrophages markedly increased. We investigated the effects of the JAK2 inhibitor RUX on M2 differentiation induced with MM tumor cells. After exposure to a low concentration of RUX, the percentage of M2 cells decreased when the monocytes were co-cultured with MM tumor cells. Trib1 gene expression of the monocytes treated with RUX was also notably reduced compared with cells not treated with the JAK2 inhibitor. Using our human MM xenograft model LAGκ-2, RUX (1.5mg/kg) reduced tumor growth and decreased the proportion of M2 macrophages in the tumor tissue of MM tumor-bearing SCID mice. Conclusion: M2 cells are present at high levels in BM derived from MM pts with PD compared to those in CR, MM cells induce monocytes to become M2 macrophages and increase Trib1 gene expression. This induces monocyte differentiation into M2 macrophages that support MM tumor cell growth.. Notably, the JAK2 inhibitor RUX inhibits both M2 macrophage polarization and Trib1 gene expression in MM, and reduces tumor growth in SCID mice bearing human MM. These results suggest that RUX may be effective for treating MM pts. Disclosures No relevant conflicts of interest to declare.

scholarly journals The chemotaxis of M1 and M2 macrophages is regulated by different chemokines

2014 ◽  
Vol 97 (1) ◽  
pp. 61-69 ◽  
Author(s):  
Wenjuan Xuan ◽  
Qing Qu ◽  
Biao Zheng ◽  
Sidong Xiong ◽  
Guo-Huang Fan
Keyword(s):  
M2 Macrophages ◽  
M1 And M2 Macrophages

Cap buckling as a potential mechanism of atherosclerotic plaque vulnerability

2014 ◽  
Vol 32 ◽  
pp. 210-224 ◽  
Author(s):  
Maria Abdelali ◽  
Steven Reiter ◽  
Rosaire Mongrain ◽  
Michel Bertrand ◽  
Philippe L. L’Allier ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Potential Mechanism ◽  
Plaque Vulnerability

scholarly journals Zoledronic acid renders human M1 and M2 macrophages susceptible to Vδ2+ γδ T cell cytotoxicity in a perforin-dependent manner

2017 ◽  
Vol 66 (9) ◽  
pp. 1205-1215 ◽  
Author(s):  
Daniel W. Fowler ◽  
John Copier ◽  
Angus G. Dalgleish ◽  
Mark D. Bodman-Smith
Keyword(s):  
T Cell ◽  
Zoledronic Acid ◽  
Dependent Manner ◽  
Cell Cytotoxicity ◽  
M2 Macrophages ◽  
Γδ T Cell ◽  
T Cell Cytotoxicity ◽  
M1 And M2 Macrophages

scholarly journals TIPS pentacene loaded PEO-PDLLA core-shell nanoparticles have similar cellular uptake dynamics in M1 and M2 macrophages and in corresponding in vivo microenvironments

2017 ◽  
Vol 13 (3) ◽  
pp. 1255-1266 ◽  
Author(s):  
Dylan K. McDaniel ◽  
Ami Jo ◽  
Veronica M. Ringel-Scaia ◽  
Sheryl Coutermarsh-Ott ◽  
Daniel E. Rothschild ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Core Shell ◽  
M2 Macrophages ◽  
Shell Nanoparticles ◽  
Core Shell Nanoparticles ◽  
M1 And M2 Macrophages
Sign in / Sign up

Export Citation Format

Share Document