scholarly journals Deactivation of 12(S)-HETE through (ω-1)-hydroxylation and β-oxidation in alternatively activated macrophages

2018 ◽  
Vol 59 (4) ◽  
pp. 615-624 ◽  
Author(s):  
Tamas Kriska ◽  
Michael J. Thomas ◽  
John R. Falck ◽  
William B. Campbell
Keyword(s):  
Cytochrome P450 ◽  
Angiotensin Ii ◽  
Oxidation Products ◽  
Eicosatetraenoic Acid ◽  
Pcr Analysis ◽  
Experimental Hypertension ◽  
M2 Macrophages ◽  
Cytochrome P450 Enzymes ◽  
M1 Macrophages ◽  
Alternatively Activated

Polarization of macrophages to proinflammatory M1 and to antiinflammatory alternatively activated M2 states has physiological implications in the development of experimental hypertension and other pathological conditions. 12/15-Lipoxygenase (12/15-LO) and its enzymatic products 12(S)- and 15(S)-hydroxyeicosatetraenoic acid (HETE) are essential in the process since disruption of the gene encoding 12/15-LO renders the mice unsusceptible to hypertension. The objective was to test the hypothesis that M2 macrophages catabolize 12(S)-HETE into products that are incapable of promoting vasoconstriction. Cultured M2 macrophages metabolized externally added [14C]12(S)-HETE into more polar metabolites, while M1 macrophages had little effect on the catabolism. The major metabolites were identified by mass spectrometry as (ω-1)-hydroxylation and β-oxidation products. The conversion was inhibited by both peroxisomal β-oxidation inhibitor, thioridazine, and cytochrome P450 inhibitors. Quantitative PCR analysis confirmed that several cytochrome P450 enzymes (CYP2E1 and CYP1B1) and peroxisomal β-oxidation markers were upregulated upon M2 polarization. The identified 12,19-dihydroxy-5,8,10,14-eicosatetraenoic acid and 8-hydroxy-6,10-hexadecadienoic acid metabolites were tested on abdominal aortic rings for biological activity. While 12(S)-HETE enhanced vasoconstrictions to angiotensin II from 15% to 25%, the metabolites did not. These results indicate that M2, but not M1, macrophages degrade 12(S)-HETE into products that no longer enhance the angiotensin II-induced vascular constriction, supporting a possible antihypertensive role of M2 macrophages.

scholarly journals Molecular Cloning and Identification of NADPH Cytochrome P450 Reductase from Panax ginseng

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6654
Author(s):  
Xian Zou ◽  
Yue Zhang ◽  
Xu Zeng ◽  
Tuo Liu ◽  
Gui Li ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Panax Ginseng ◽  
Pcr Analysis ◽  
Cytochrome P450 Reductase ◽  
Cytochrome P450 Enzymes ◽  
Phylogenetic Tree Analysis ◽  
Nadph Cytochrome ◽  
P450 Reductase ◽  
Meja Treatment ◽  
Nadph Cytochrome P450 Reductase

Ginseng (Panax ginseng C.A. Mey.) is a precious Chinese traditional medicine, for which ginsenosides are the most important medicinal ingredients. Cytochrome P450 enzymes (CYP450) and their primary redox molecular companion NADPH cytochrome P450 reductase (CPR) play a key role in ginsenoside biosynthesis pathway. However, systematic studies of CPR genes in ginseng have not been reported. Numerous studies on ginsenoside synthesis biology still use Arabidopsis CPR (AtCPR1) as a reductase. In this study, we isolated two CPR genes (PgCPR1, PgCPR2) from ginseng adventitious roots. Phylogenetic tree analysis showed that both PgCPR1 and PgCPR2 are grouped in classⅡ of dicotyledonous CPR. Enzyme experiments showed that recombinant proteins PgCPR1, PgCPR2 and AtCPR1 can reduce cytochrome c and ferricyanide with NADPH as the electron donor, and PgCPR1 had the highest enzymatic activities. Quantitative real-time PCR analysis showed that PgCPR1 and PgCPR2 transcripts were detected in all examined tissues of Panax ginseng and both showed higher expression in stem and main root. Expression levels of the PgCPR1 and PgCPR2s were both induced after a methyl jasmonate (MeJA) treatment and its pattern matched with ginsenoside accumulation. The present investigation suggested PgCPR1 and PgCPR2 are associated with the biosynthesis of ginsenoside. This report will assist in future CPR family studies and ultimately improving ginsenoside production through transgenic engineering and synthetic biology.

scholarly journals Macrophages in Tumor Microenvironments and the Progression of Tumors

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Ning-Bo Hao ◽  
Mu-Han Lü ◽  
Ya-Han Fan ◽  
Ya-Ling Cao ◽  
Zhi-Ren Zhang ◽  
...  
Keyword(s):  
Adaptive Immune Response ◽  
M2 Macrophages ◽  
Tumor Associated Macrophages ◽  
M1 Macrophages ◽  
Tumor Microenvironments ◽  
Adaptive Immune ◽  
Immunosuppressive Microenvironment ◽  
Inflammatory Molecules ◽  
Alternatively Activated ◽  
Classically Activated

Macrophages are widely distributed innate immune cells that play indispensable roles in the innate and adaptive immune response to pathogens and in-tissue homeostasis. Macrophages can be activated by a variety of stimuli and polarized to functionally different phenotypes. Two distinct subsets of macrophages have been proposed, including classically activated (M1) and alternatively activated (M2) macrophages. M1 macrophages express a series of proinflammatory cytokines, chemokines, and effector molecules, such as IL-12, IL-23, TNF-α, iNOS and MHCI/II. In contrast, M2 macrophages express a wide array of anti-inflammatory molecules, such as IL-10, TGF-β, and arginase1. In most tumors, the infiltrated macrophages are considered to be of the M2 phenotype, which provides an immunosuppressive microenvironment for tumor growth. Furthermore, tumor-associated macrophages secrete many cytokines, chemokines, and proteases, which promote tumor angiogenesis, growth, metastasis, and immunosuppression. Recently, it was also found that tumor-associated macrophages interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. So mediating macrophage to resist tumors is considered to be potential therapy.

scholarly journals Macrophage Innate Training Induced by IL-4 Activation Enhances OXPHOS Driven Anti-Mycobacterial Responses

2021 ◽  
Author(s):  
Mimmi L. E. Lundahl ◽  
Morgane Mitermite ◽  
Dylan G. Ryan ◽  
Niamh C. Williams ◽  
Ming Yang ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Mycobacterial Infection ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Cytokine Responses ◽  
M1 Macrophage ◽  
Mycobacterial Growth ◽  
Insight Into ◽  
Alternatively Activated ◽  
Classically Activated

AbstractMacrophages are key innate immune cells for determining the outcome of Mycobacterium tuberculosis infection. Polarization with IFNγ and LPS into the “classically activated” M1 macrophage enhances pro-inflammatory and microbicidal responses, important for eradicating the bacterium. By contrast, “alternatively activated” M2 macrophages, polarized with IL-4, oppose bactericidal mechanisms and allow mycobacterial growth. These activation states are accompanied by distinct metabolic profiles, where M1 macrophages favor near exclusive use of glycolysis, whereas M2 macrophages up-regulate oxidative phosphorylation (OXPHOS). Here we demonstrate that activation with IL-4 counterintuitively induces protective innate memory against mycobacterial challenge. This was associated with enhanced pro-inflammatory cytokine responses and killing capacity. Moreover, despite this switch towards a phenotype that is more akin to classical activation, IL-4 trained macrophages do not demonstrate M1-typical metabolism, instead retaining heightened use of OXPHOS. Moreover, inhibition of OXPHOS with oligomycin, 2-deoxy glucose or BPTES all impeded heightened pro-inflammatory cytokine responses from IL-4 trained macrophages. Lastly, this work identifies that IL-10 negatively regulates protective IL-4 training, impeding pro-inflammatory and bactericidal mechanisms. In summary, this work provides new and unexpected insight into alternative macrophage activation states in the context of mycobacterial infection.

scholarly journals Defects in Macrophage Reprogramming in Cancer Therapy: The Negative Impact of PD-L1/PD-1

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao Cai ◽  
Yichi Zhang ◽  
Jian Wang ◽  
Jinyang Gu
Keyword(s):  
Cancer Therapy ◽  
Negative Impact ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Programmed Death ◽  
Antigen Presenting ◽  
Cell Death Protein ◽  
Alternatively Activated

Classically activated M1 macrophages and alternatively activated M2 macrophages are two polarized subsets of macrophages at the extreme ends of a constructed continuum. In the field of cancer research, M2 macrophage reprogramming is defined as the repolarization of pro-tumoral M2 to anti-tumoral M1 macrophages. It is known that colony-stimulating factor 1 (CSF1)/CSF1 receptor (CSF1R) and CSF2/CSF2R signaling play important roles in macrophage polarization. Targeting CSF1/CSF1R for M2 macrophage reprogramming has been widely performed in clinical trials for cancer therapy. Other targets for M2 macrophage reprogramming include Toll-like receptor 7 (TLR7), TLR8, TLR9, CD40, histone deacetylase (HDAC), and PI3Kγ. Although macrophages are involved in innate and adaptive immune responses, M1 macrophages are less effective at phagocytosis and antigen presenting, which are required properties for the activation of T cells and eradication of cancer cells. Similar to T and dendritic cells, the “functionally exhausted” status might be attributed to the high expression of programmed death-ligand 1 (PD-L1) or programmed cell death protein 1 (PD-1). PD-L1 is expressed on both M1 and M2 macrophages. Macrophage reprogramming from M2 to M1 might increase the expression of PD-L1, which can be transcriptionally activated by STAT3. Macrophage reprogramming or PD-L1/PD-1 blockade alone is less effective in the treatment of most cancers. Since PD-L1/PD-1 blockade could make up for the defect in macrophage reprogramming, the combination of macrophage reprogramming and PD-L1/PD-1 blockade might be a novel treatment strategy for cancer therapy.

M2 Macrophages but not M1 Macrophages Are Associated with Worst Outcome in Classical Hodgkin Lymphoma

2014 ◽  
Vol 226 (02) ◽  
Author(s):  
M Barros ◽  
P Segges ◽  
G Vera-Lozada ◽  
R Hassan ◽  
G Niedobitek
Keyword(s):  
Hodgkin Lymphoma ◽  
M2 Macrophages ◽  
Classical Hodgkin Lymphoma ◽  
M1 Macrophages

Reparação óssea no implante dental

2020 ◽  
Vol 12 (45) ◽  
pp. 63-66
Author(s):  
Halim Nagem Filho ◽  
Reinaldo Francisco Maia ◽  
Reinaldo Missaka ◽  
Nasser Hussein Fares
Keyword(s):  
Gene Expression ◽  
Titanium Surface ◽  
Close Contact ◽  
The Other ◽  
Main Function ◽  
Indirect Interaction ◽  
M2 Macrophages ◽  
Activated Macrophages ◽  
M1 Macrophages ◽  
High Production

The osseointegration is the stable and functional union between the bone and a titanium surface. A new bone can be found on the surface of the implant about 1 week after its installation; the bone remodeling begins between 6 and 12 weeks and continues throughout life. After the implant insertion, depending on the energy of the surface, the plasma fluid immediately adheres, in close contact with the surface, promoting the adsorption of proteins and inducing the indirect interaction of the cells with the material. Macrophages are cells found in the tissues and originated from bone marrow monocytes. The M1 macrophages orchestrate the phagocytic phase in the inflammatory region and also produce inflammatory cytokines involved with the chronic inflammation and the cleaning of the wound and damaged tissues from bacteria. On the other hand, alternative-activated macrophages (M2) are activated by IL-10, the immune complex. Its main function consists on regulating negatively the inflammation through the secretion of the immunosuppressant IL-10. The M2 macrophages present involvement with the immunosuppression, besides having a low capacity for presenting antigens and high production of cytokines; these can be further divided into M2a, M2b, and M2c, based on the gene expression profile.

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