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M2 polarization

Al Shaimaa Hasan, Lan Luo, Chen Yan, Tian-Xia Zhang, Yoshishige Urata, Shinji Goto, Safwat A Mangoura, Mahmoud H Abdel-Raheem, Shouhua Zhang, Tao-Sheng Li
Cardiosphere-derived cells (CDCs), one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1) into a regulatory anti-inflammatory phenotype (M2). Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control...
2016: PloS One
Sofia Sousa, Jorma Määttä
This overview addresses the recent research developments in the role of tumour-associated macrophages (TAM) in bone metastasis biology and management of breast and prostate cancer as well as in primary and lung metastatic osteosarcoma. Immunosuppressive M2-type TAMs have been shown to associate with poor prognosis. Throughout their life cycle, macrophages (Macs) can adapt to environmental cues and influence the surroundings by secreting different cytokines and enzymes crucial to matrix remodelling, infection fighting, immune regulation and/or inflammation...
September 2016: Journal of Bone Oncology
Su-Min Lim, Hyun Sik Choi, Jin-Ju Jeong, Seung-Won Han, Dong-Hyun Kim
We investigated the effect of DWac on the gut microbiota composition in mice with 2,3,6-trinitrobenzenesulfonic acid- (TNBS-) induced colitis. Treatment with DWac restored TNBS-disturbed gut microbiota composition and attenuated TNBS-induced colitis. Moreover, we examined the effect of DWac in mice with mesalazine-resistant colitis (MRC). Intrarectal injection of TNBS in MRC mice caused severe colitis, as well as colon shortening, edema, and increased myeloperoxidase activity. Treatment with mesalazine (30 mg/kg) did not attenuate TNBS-induced colitis in MRC mice, whereas treatment with DWac (30 mg/kg) significantly attenuated TNBS-induced colitis...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Daniel Hachim, Samuel T LoPresti, Cecelia C Yates, Bryan N Brown
The present study tests the hypothesis that transient, early-stage shifts in macrophage polarization at the tissue-implant interface from a pro-inflammatory (M1) to an anti-inflammatory/regulatory (M2) phenotype mitigates the host inflammatory reaction against a non-degradable polypropylene mesh material and improves implant integration downstream. To address this hypothesis, a nanometer-thickness coating capable of releasing IL-4 (an M2 polarizing cytokine) from an implant surface at early stages of the host response has been developed...
October 11, 2016: Biomaterials
Xingwei Jiang, Tingting Zhou, Yan Xiao, Jiahui Yu, Shuaijie Dou, Guojiang Chen, Renxi Wang, He Xiao, Chunmei Hou, Wei Wang, Qingzhu Shi, Jiannan Feng, Yuanfang Ma, Beifen Shen, Yan Li, Gencheng Han
T cell Ig mucin-3 (Tim-3), an immune checkpoint inhibitor, shows therapeutic potential. However, the molecular mechanism by which Tim-3 regulates immune responses remains to be determined. In particular, very little is known about how Tim-3 works in innate immune cells. Here, we demonstrated that Tim-3 is involved in the development of tumor-promoting M2 macrophages in colon cancer. Manipulation of the Tim-3 pathway significantly affected the polarization status of intestinal macrophages and the progression of colon cancer...
2016: Oncoimmunology
Matthias Holzlechner, Katharina Strasser, Elitsa Zareva, Luise Steinhaeuser, Hanna Birnleitner, Andrea Beer, Michael Bergmann, Rudolf Oehler, Martina Marchetti-Deschmann
Tissue-resident immune cells differ from the corresponding blood cells in many functional aspects. Although the proteome of blood immune cells is well investigated there are almost no data on tissue-resident immune cells. Here we explored the potential of MALDI-TOF-MS imaging (MSI) to investigate these cells in colon tissue, which exhibits a strong immune infiltration. MSI identified several proteinaceous markers that colocalized with specific structures of the colon such as mucosa or muscularis mucosae in six patients...
October 18, 2016: Journal of Proteome Research
Lien M Dos Santos, Tatiane M da Silva, Juliana H Azambuja, Priscila T Ramos, Pathise S Oliveira, Elita F da Silveira, Nathalia S Pedra, Kennia Galdino, Carlus A T do Couto, Mayara S P Soares, Rejane G Tavares, Roselia M Spanevello, Francieli M Stefanello, Elizandra Braganhol
Methionine is an essential amino acid involved in critical metabolic process, and regulation of methionine flux through metabolism is important to supply this amino acid for cell needs. Elevation in plasma methionine commonly occurs due to mutations in methionine-metabolizing enzymes, such as methionine adenosyltransferase. Hypermethioninemic patients exhibit clinical manifestations, including neuronal and liver disorders involving inflammation and tissue injury, which pathophysiology is not completely established...
October 17, 2016: Molecular and Cellular Biochemistry
Min Zhang, Zhongqi Zhou, Jinguang Wang, Shufa Li
Inflammatory pathways play an important role in impaired glucose metabolism and insulin production. Adipose tissue inflammation is characterized by infiltration and expansion of macrophages, leading to type 2 diabetes (T2D). Macrophage polarization contributes to various inflammatory responses and cytokine production profiles. MiR-130b is involved in regulating immune response and metabolism. However, the specific role in macrophage polarization and glucose metabolism of T2D has not been reported. In this study, C57BL/6 mice were fed a high-fat diet to induce T2D mice model...
October 13, 2016: Immunology Letters
Ming-Zhi Zhang, Xin Wang, Yinqiu Wang, Aolei Niu, Suwan Wang, Chenhang Zou, Raymond C Harris
Cytokines IL-4 and IL-13 play important roles in polarization of macrophages/dendritic cells to an M2 phenotype, which is important for recovery from acute kidney injury. Both IL-4 and IL-13 activate JAK3/STAT6 signaling. In mice with diphtheria toxin receptor expression in proximal tubules (selective injury model), a relatively selective JAK3 inhibitor, tofacitinib, led to more severe kidney injury, delayed recovery from acute kidney injury, increased inflammatory M1 phenotype markers and decreased reparative M2 phenotype markers of macrophages/dendritic cells, and development of more severe renal fibrosis after diphtheria toxin administration...
October 10, 2016: Kidney International
Hao Meng, Yuan Liu, Bruce P Lee
: Mussel adhesive moiety, catechol, has been utilized to design a wide variety of biomaterials. However, the biocompatibility and biological responses associated with the byproducts generated during the curing process of catechol has never been characterized. An in situ curable polymer model system, 4-armed polyethylene glycol polymer end-capped with dopamine (PEG-D4), was used to characterize the production of hydrogen peroxide (H2O2) during the oxidative crosslinking of catechol. Although PEG-D4 cured rapidly (under 30s), catechol continues to polymerize over several hours to form a more densely crosslinked network over time...
October 12, 2016: Acta Biomaterialia
Kristi J Warren, Xi Fang, Nagaraj M Gowda, Joshua J Thompson, Nicola M Heller
Lung M2 macrophages are regulators of airway inflammation, associated with poor lung function in allergic asthma. Previously, we demonstrated that IL-4-induced M2 gene expression correlated with tyrosine phosphorylation of the insulin receptor substrate (IRS)-2 in macrophages. We hypothesized that negative regulation of IRS-2 activity following IL-4 stimulation is dependent upon serine phosphorylation of IRS-2. Herein, we describe an inverse relationship between tyrosine phosphorylation (pY) and serine phosphorylation (pS) of IRS-2 following IL-4 stimulation...
October 14, 2016: Journal of Biological Chemistry
JoAnn Trial, Lawrence A Potempa, Mark L Entman
The participation of C-reactive protein (CRP) in host defense against microorganisms has been well described. More controversial has been its role in chronic conditions such as cardiovascular disease. Our recent publications explain the reasons for some of the confusion concerning CRP as a risk factor for disease and whether it is pro-inflammatory or anti-inflammatory. We found that two isoforms of CRP, pentameric (pCRP) and monomeric (mCRP), on microparticles (MPs), were not measureable by standard clinical assays...
2016: Inflammation and Cell Signaling
Kaitlyn Sadtler, Brian W Allen, Kenneth Estrellas, Franck Housseau, Drew M Pardoll, Jennifer H Elisseeff
The immune system mediates tissue growth and homeostasis and is the first responder to injury or biomaterial implantation. Recently, it has been appreciated that immune cells play a critical role in wound healing and tissue repair and should thus be considered as potentially beneficial particularly in the context of scaffolds for regenerative medicine. Here, we present a flow cytometric analysis of cellular recruitment to tissue-derived extracellular matrix scaffolds where we quantitatively describe the infiltration and polarization of several immune subtypes including macrophages, dendritic cells, neutrophils, monocytes, T cells, and B cells...
October 13, 2016: Tissue Engineering. Part A
Philipp Lohneis, Stephan Wienert, Frederick Klauschen, Ioannis Anagnostopoulos, Korinna Jöhrens
There is evidence from studies on fibrotic diseases that a TH2 polarized immune response, characterized by the production of cytokines like IL-4, IL-5, and IL-13 is important for fibrosis development. Data concerning the role of TH2 polarized immune response for fibrogenesis in lymphomas are scarce. Using immunohistochemistry, we investigated paraffin embedded tissue specimens of 58 follicular lymphomas (FL) grade 1/2 with and without fibrosis. In FL with fibrosis, we detected more interfollicular GATA-3 positive lymphocytes and a shift towards a TH2 immune response...
October 13, 2016: Leukemia & Lymphoma
Line S Bisgaard, Christina K Mogensen, Alexander Rosendahl, Helena Cucak, Lars Bo Nielsen, Salka E Rasmussen, Tanja X Pedersen
Macrophages are heterogeneous and can polarize into specific subsets, e.g. pro-inflammatory M1-like and re-modelling M2-like macrophages. To determine if peritoneal macrophages (PEMs) or bone marrow derived macrophages (BMDMs) resembled aortic macrophages from ApoE-/- mice, their M1/M2 phenotype, inflammatory status, and lipid metabolism signatures were compared. oxLDL accumulation was similar in PEMs and BMDMs. On protein expression level, BMDMs showed an M2-like CD206(high)CD11c(low) profile, while cholesterol loading led to enhanced CD11c expression and reduced MCP-1 secretion...
October 13, 2016: Scientific Reports
Tetsuya Kimura, Shigeyuki Nada, Noriko Takegahara, Tatsusada Okuno, Satoshi Nojima, Sujin Kang, Daisuke Ito, Keiko Morimoto, Takashi Hosokawa, Yoshitomo Hayama, Yuichi Mitsui, Natsuki Sakurai, Hana Sarashina-Kida, Masayuki Nishide, Yohei Maeda, Hyota Takamatsu, Daisuke Okuzaki, Masaki Yamada, Masato Okada, Atsushi Kumanogoh
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...
October 12, 2016: Nature Communications
Tao Yan, Poornima Venkat, Michael Chopp, Alex Zacharek, Ruizhuo Ning, Cynthia Roberts, Yi Zhang, Mei Lu, Jieli Chen
BACKGROUND AND PURPOSE: Comorbidity of diabetes mellitus and stroke results in worse functional outcome, poor long-term recovery, and extensive vascular damage. We investigated the neurorestorative effects and mechanisms of stroke treatment with human bone marrow-derived mesenchymal stromal cells (hMSCs) in type 2 diabetes mellitus (T2DM) rats. METHODS: Adult male Wistar rats were induced with T2DM, subjected to 2 hours of middle cerebral artery occlusion (MCAo) and treated via tail-vein injection with (1) PBS (n=8) and (2) hMSCs (n=10; 5×10(6)) at 3 days after MCAo...
October 11, 2016: Stroke; a Journal of Cerebral Circulation
Sara Bermudez, Guzal Khayrullina, Yujia Zhao, Kimberly R Byrnes
Spinal cord injury (SCI) results in both acute and chronic inflammation, as a result of activation of microglia, invasion of macrophages and activation of the NADPH oxidase (NOX) enzyme. The NOX enzyme is a primary source of reactive oxygen species (ROS) and is expressed by microglia and macrophages after SCI. These cells can assume either a pro- (M1) or anti-inflammatory (M2) polarization phenotype and contribute to tissue response to SCI. However, the contribution of NOX expression and ROS production to this polarization and vice versa is currently undefined...
October 8, 2016: Molecular and Cellular Neurosciences
Manishekhar Kumar, Jeannine M Coburn, David L Kaplan, Biman B Mandal
Macrophages, the key players in immunoregulation, are actively involved in tissue remodelling and vascularization. Recent advances in tissue engineering and regenerative medicine illustrate the importance of 'immuno-informed' biomaterials to regulate the microenvironment of biomedical implants. In the current study, silk-based 3D hydrogels were utilized to regulate cytokine delivery for macrophage, a type of immune cell, differentiation and polarization. Three different hydrogel variants, silk-poly(ethylene glycol) (PEG) (SP), silk-horseradish peroxidase (HRP) (SH) and silk-sonicated (SS) hydrogels were studied...
October 11, 2016: ACS Applied Materials & Interfaces
Hui Shi, Kuang Zheng, Zulu Su, Hai Su, Ming Zhong, Xuenong He, Changlong Zhou, Hao Chen, Qijiang Xiong, Yi Zhang
Microglia polarization plays a vital role in brain inflammatory injury following intracerebral hemorrhage (ICH). Previous studies have shown that sinomenine possesses potential immunoregulatory capabilities. However, microglia polarization's exact mechanisms in ICH remain uncertain. Therefore, we examined the role of sinomenine on microglia polarization and brain inflammation following ICH. For the experiment, autologous blood models were constructed in C57/BL6 mice. Markers of classically activated (M1) and alternatively activated (M2) microglia were detected by real-time polymerase chain reaction, immunofluorescence, and flow cytometry...
October 15, 2016: Journal of Neuroimmunology
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