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Nathan Goodyear

Regulatory Mechanisms for Adipose Tissue M1 and M2 Macrophages in Diet-Induced Obese Mice - 0 views

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    M1 macrophages (and a high M1/M2 ratio) promote inflammation and insulin resistance in obese individuals; This is in contrast to M2 macrophages.  Obese individuals will see a shift in M2 to M1.  The exact mechanism is yet unknown.  But M2 macrophages have been shown to resolve insulin resistance in this obese mice model
Nathan Goodyear

Exploring the basic science of prolapse meshes - 0 views

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    Mesh implantation, here in the vaginal area, increases both M1 and M2 maturation migration. M1 increases pro-inflammatory signaling and processes and M2 promotes remodeling/healing... Both increase, but M1 increases more than M2 proportionally. M2 can increase the bridge scaring that can occur as well as the potential for immune suppression and autoimmune/cancer implications
Nathan Goodyear

Inhibition of TGF-β induced lipid droplets switches M2 macrophages to M1 phen... - 0 views

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    Not specifically on cancer, but inhibition of TGF-beta promotes M2 to M1 polarization. It is one thing to show that TGF-beta stimulates M2 polarization; it is quite another to show the opposite. Significantly relevant in the TME cancer debate.
Nathan Goodyear

M2 macrophages exhibit higher sensitivity to oxLDL-induced lipotoxicity than other mono... - 0 views

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    macrophages (M1) in obese individuals are more pro-inflammatory than those in lean (M2) individuals. The exact mechanism to explain the switch from M2 to M1 has yet to be determined, but this study proposes that lipotoxic oxidized LDL is a possible target
Nathan Goodyear

Different distributions of M1 and M2 macrophages in a mouse model of laser-induced chor... - 0 views

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    There are two subtypes of macrophages, M1 and M2 (8,9). M1, or pro-inflammatory macrophages, are considered to be important for the destruction of tumor cells and foreign organisms, whereas M2, or anti-inflammatory macrophages, have been suggested to be primarily involved in angiogenesis, wound healing, chronic infections, tumorigenesis and tumor metastasis
Nathan Goodyear

M2 to M1; macrophage reprogramming can be done! - 0 views

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    M2 to M1 polarization is possible.
Nathan Goodyear

American Journal of Obstetrics & Gynecology Home Page - 0 views

  • M1 macrophages are characterized by the secretion of reactive oxygen species and proinflammatory cytokines and chemokines and can be identified via the cell surface marker CD86
  • M2 macrophages secrete growth factors and antiinflammatory immune modulators and can be identified by the cell surface marker CD206
  • an overzealous M2 response can also lead to excess tissue deposition and fibrosis
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  • Studies of similar meshes that are used in hernia repair have demonstrated that all polypropylene meshes induce a prolonged inflammatory response at the site of implantation
  • the long-term presence of activated inflammatory cells, such as macrophages at the mesh tissue interface, can impact negatively the ability of the mesh to function as intended.
  • All M1 proinflammatory and M2 proremodeling cytokines and chemokines were increased in mesh explants as compared with nonmesh tissue (Table 3Table 3), which indicated a robust, active, and ongoing host response to polypropylene long after implantation
  • Comparison of the ratio of the M2 proremodeling cytokines (IL-10+IL-4) with the M1 proinflammatory cytokines (TNF-α+IL-12p70) revealed a decrease in mesh explants as compared with controls (P = .003), which indicated a shift towards a proinflammatory profile.
  • Mesh explants contained a higher number of total cells/×200 field when compared with controls (682.46 ± 142.61 cells vs 441.63 ± 126.13 cells; P < .001) and a lower ratio of M2:M1 macrophages (0.260 ± 0.161 cells vs 1.772 ± 1.919; P = .001), which supported an ongoing proinflammatory response.
  • the host response was proportional to the amount of material in contact with the host
  • A persistent foreign body response was observed in mesh-tissue complexes that were excised from women who required surgical excision of mesh months to years after mesh implantation
  • The host response was characterized by a predominance of macrophages with an increase in both proinflammatory and proremodeling cytokines/chemokines along with increased tissue degradation, as evidenced by increased MMP-2 and -9
  • Mesh-tissue complexes removed for mesh exposure had increased pro–MMP-9 that indicated a proinflammatory and tissue destruction–type response
  • The presence of macrophages, elevated cytokines, chemokines, and MMPs in tissue-mesh complexes that were excised from patients with exposure or pain suggests that polypropylene mesh elicits an ongoing host inflammatory response
  • In the presence of a permanent foreign body, the implant is surrounded with a fibrotic capsule because it cannot be degraded
  • For hernia meshes, if the fibers are too close (<1 mm), the fibrotic response to neighboring fibers overlaps, or “bridges,” and results in “bridging fibrosis” or encapsulation of the mesh
  • Gynemesh PS has a highly unstable geometry when loaded that resulted in pore collapse and increasing stiffness of the product
  • mesh shrinkage (50-70%) has been described to occur after transvaginal insertion of prolapse meshes
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    Mesh and the abnormal immune response.
Nathan Goodyear

TGF-β1 secreted by M2 phenotype macrophages enhances the stemness and migrati... - 0 views

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    T-regulator cells secrete TGF-beta to promote M2 polarization in the TME to promote tumor progression and spread.
Nathan Goodyear

Frontiers | Modulators of the Balance between M1 and M2 Macrophages during Pregnancy | ... - 0 views

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    Great review of M1 and M2 polarization in pregnancy. The implication for me is the impact in the TME in cancer and its contribution to physical and immune escape.
Nathan Goodyear

Hydroxychloroquine induced lung cancer suppression by enhancing chemo-sensitization and... - 0 views

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    Hydroxychloroquine induces M2 to M1 Macrophage polarization.
Nathan Goodyear

Tumor-derived lactate induces M2 macrophage polarization via the activation of the ERK/... - 0 views

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    Lactate stimulates M2 macrophage polarization in the TME via ERK/STAT3 activation.
Nathan Goodyear

Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves imm... - 0 views

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    Chemotherapy increases TAMs in the primary tumors. These TAMs suppresses the anti-cancer cytotoxicity of T cells. The authors here describe both TAMs and TIMs. TAMs are the M1/M2 most often discussed. M2 TAMs increase Tumor Infiltrating Macrophages (TIMs) which increase local immunosuppression and chemotherapy resistance.
Nathan Goodyear

Chemotherapy Alters Monocyte Differentiation to Favor Generation of Cancer-Supporting M... - 0 views

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    Chemotherapy induces M2 polarization in the TME
Nathan Goodyear

TGFβ signaling plays a critical role in promoting alternative macrophage acti... - 0 views

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    TGF-beta promotes M2 polarization through epigenetic expression that effects TME and tumor growth potential.
Nathan Goodyear

Hydroxychloroquine induced lung cancer suppression by enhancing chemo-sensitization and... - 0 views

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    hydroxychloroquine induces chemo-sensitivity and pushes M2 to M1 macrophage polarization. Effects occur within the TME to increase CD8+ activity within the TME.
Nathan Goodyear

Adipose tissue macrophages: p... [Curr Opin Clin Nutr Metab Care. 2011] - PubMed - NCBI - 0 views

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    adipose tissue changes the macrophage type from M2 to M1 dominance.  This reveals the microenvironment found in adipose tissue and the effect on the adipose tissue macrophages.
Nathan Goodyear

Obesity induces a phenotypic switch in adipose tissue macrophage polarization - 0 views

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    obesity results in shift from M2 macrophages to M1 macrophages.  This results in inflammation and insulin resistance.  This fits the current hypothesis that obesity is in and of itself an inflammatory condition.
Nathan Goodyear

JCI - Inflammatory links between obesity and metabolic disease - 0 views

  • metainflammation
  • The chronic nature of obesity produces a tonic low-grade activation of the innate immune system that affects steady-state measures of metabolic homeostasis over time
  • It is clear that inflammation participates in the link between obesity and disease
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  • Multiple inflammatory inputs contribute to metabolic dysfunction, including increases in circulating cytokines (10), decreases in protective factors (e.g., adiponectin; ref. 11), and communication between inflammatory and metabolic cells
  • adipose tissue macrophage (ATM)
  • Physiologic enhancement of the M2 pathways (e.g., eosinophil recruitment in parasitic infection) also appears to be capable of reducing metainflammation and improving insulin sensitivity (27).
  • increasing adiposity results in a shift in the inflammatory profile of ATMs as a whole from an M2 state to one in which classical M1 proinflammatory signals predominate (21–23).
  • The M2 activation state is intrinsically linked to the activity of PPARδ and PPARγ
  • well-known regulators of lipid metabolism and mitochondrial activity
  • Independent of obesity, hypothalamic inflammation can impair insulin release from β cells, impair peripheral insulin action, and potentiate hypertension (63–65).
  • inflammation in pancreatic islets can reduce insulin secretion and trigger β cell apoptosis leading to decreased islet mass, critical events in the progression to diabetes (33, 34)
  • Since an estimated excess of 20–30 million macrophages accumulate with each kilogram of excess fat in humans, one could argue that increased adipose tissue mass is de facto a state of increased inflammatory mass
  • JNK, TLR4, ER stress)
  • NAFLD is associated with an increase in M1/Th1 cytokines and quantitative increases in immune cells
  • Upon stimulation by LPS and IFN-γ, macrophages assume a classical proinflammatory activation state (M1) that generates bactericidal or Th1 responses typically associated with obesity
  • DIO, metabolites such as diacylglycerols and ceramides accumulate in the hypothalamus and induce leptin and insulin resistance in the CNS (58, 59)
  • saturated FAs, which activate neuronal JNK and NF-κB signaling pathways with direct effects on leptin and insulin signaling (60)
  • Lipid infusion and a high-fat diet (HFD) activate hypothalamic inflammatory signaling pathways, resulting in increased food intake and nutrient storage (57)
  • Maternal obesity is associated with endotoxemia and ATM accumulation that may affect the developing fetus (73)
  • Placental inflammation is a characteristic of maternal obesity
  • a risk factor for obesity in offspring, and involves inflammatory macrophage infiltration that can alter the maternal-fetal circulation (74
  • Of these PRRs, TLR4 has received the most attention, as this receptor can be activated by free FAs to generate proinflammatory signals and activate NF-κB
  • Nod-like receptor (NLR) family of PRRs
  • ceramides and sphingolipids
  • The adipokine adiponectin has long been recognized to have positive benefits on multiple cell types to promote insulin sensitivity and deactivate proinflammatory pathways.
  • adiponectin stimulates ceramidase activity and modulates the balance between ceramides and sphingosine-1-phosphate
  • Inhibition of ceramide production blocks the ability of saturated FAs to induce insulin resistance (101)
  • NF-κB, obesity also activates JNK in insulin-responsive tissues
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    must read to see our current knowledge on the link between inflammation and obesity.
Nathan Goodyear

The Role of Macrophage Polarization in Infectious and Inflammatory Diseases - 0 views

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    Good read/discussion on the maturation process of M1, M2 and their interaction with the Th1 and Th2 signaling in infections and inflammation: think autoimmune disease, chronic disease, and cancer.
Nathan Goodyear

Acidity promotes tumour progression by altering macrophage phenotype in prostate cancer... - 0 views

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    The acidic pH of the TME induces M2 polarization.
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