Obesity and insulin resistance are closely associated with chronic inflammation in adipose tissue, where macrophages play an important role. Adipose tissue macrophages can be divided into two main phenotypes: the classical M1 macrophages and alternatively activated macrophages M2. M1 macrophages produce pro-inflammatory cytokines (TNF-α, interleukin IL-6 and MCP-1) and thus contribute to the development of insulin resistance. On the other hand, M2 macrophages, anti-inflammatory, are involved in the maintenance of tissue homeostasis and are typical in the adipose tissue of slender individuals. Macrophages can also play a role in the pathogenesis of other serious illnesses such as cardiovascular diseases or cancer. This article reviews the latest data on macrophage polarization in adipose tissue.

• MeSH
• chemokin CCL2 metabolismus   MeSH
• fenotyp MeSH
• hypoxie metabolismus   patologie   MeSH
• interleukin-6 metabolismus   MeSH
• inzulinová rezistence fyziologie   MeSH
• lidé MeSH
• makrofágy patologie   MeSH
• obezita metabolismus   patologie   MeSH
• TNF-alfa metabolismus   MeSH
• tuková tkáň patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• Publikační typ
• abstrakt z konference MeSH

Berberine (BBR), a small molecule protoberberine isoquinoline alkaloid, is easy to cross the blood-brain barrier and is a potential drug for neurodegenerative diseases. Here, we explored the role and molecular mechanism of BBR in Alzheimer's disease (AD) progression. Weighted gene co-expression network analysis (WGCNA) was conducted to determine AD pathology-associated gene modules and differentially expressed genes (DEGs) were also identified. GO and KEGG analyses were performed for gene function and signaling pathway annotation. Cell counting kit-8 (CCK8) assay was applied to analyze cell viability. Immunofluorescence (IF) staining assay was conducted to measure the levels of polarization markers. The production of inflammatory cytokines was analyzed by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) were detected using a ROS detection kit and a MMP Detection Kit (JC-1), respectively. AD pathology-associated DEGs were applied for GO function annotation and KEGG enrichment analysis, and the results uncovered that AD pathology was related to immune and inflammation. Lipopolysaccharide (LPS) exposure induced the M1 phenotype of microglia, and BBR suppressed LPS-induced M1 polarization and induced microglia toward M2 polarization. Through co-culture of microglia and neuronal cells, we found that BBR exerted a neuro-protective role by attenuating the injury of LPS-induced HMC3 on SH-SY5Y cells. Mechanically, BBR switched the M1/M2 phenotypes of microglia by activating PI3K-AKT signaling. In summary, BBR protected neuronal cells from activated microglia-mediated neuro-inflammation by switching the M1/M2 polarization in LPS-induced microglia via activating PI3K-AKT signaling. Key words Alzheimer's Disease, Berberine, Microglia polarization, Neuroinflammation, PI3K-AKT signaling.

• MeSH
• Alzheimerova nemoc * metabolismus   farmakoterapie   patologie   MeSH
• berberin * farmakologie   terapeutické užití   MeSH
• fosfatidylinositol-3-kinasy * metabolismus   MeSH
• lidé MeSH
• mikroglie * účinky léků   metabolismus   MeSH
• myši MeSH
• neuroprotektivní látky * farmakologie   MeSH
• polarita buněk účinky léků   MeSH
• protoonkogenní proteiny c-akt * metabolismus   MeSH
• signální transdukce * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Macrophages represent heterogeneous cell population with important roles in defence mechanisms and in homoeostasis. Tissue macrophages from diverse anatomical locations adopt distinct activation states. M1 and M2 macrophages are two polarized forms of mononuclear phagocyte in vitro differentiation with distinct phenotypic patterns and functional properties, but in vivo, there is a wide range of different macrophage phenotypes in between depending on the microenvironment and natural signals they receive. In human infections, pathogens use different strategies to combat macrophages and these strategies include shaping the macrophage polarization towards one or another phenotype. Macrophages infiltrating the tumours can affect the patient's prognosis. M2 macrophages have been shown to promote tumour growth, while M1 macrophages provide both tumour-promoting and anti-tumour properties. In autoimmune diseases, both prolonged M1 activation, as well as altered M2 function can contribute to their onset and activity. In human atherosclerotic lesions, macrophages expressing both M1 and M2 profiles have been detected as one of the potential factors affecting occurrence of cardiovascular diseases. In allergic inflammation, T2 cytokines drive macrophage polarization towards M2 profiles, which promote airway inflammation and remodelling. M1 macrophages in transplantations seem to contribute to acute rejection, while M2 macrophages promote the fibrosis of the graft. The view of pro-inflammatory M1 macrophages and M2 macrophages suppressing inflammation seems to be an oversimplification because these cells exploit very high level of plasticity and represent a large scale of different immunophenotypes with overlapping properties. In this respect, it would be more precise to describe macrophages as M1-like and M2-like.

• MeSH
• buněčná diferenciace MeSH
• cytokiny * MeSH
• fenotyp MeSH
• lidé MeSH
• makrofágy * MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Activation of microglia is considered the most important component of neuroinflammation. Microglia can adopt a pro-inflammatory (M1) or anti-inflammatory (M2) phenotype. Opioid receptors (ORs) have been shown to control neurotransmission of various peptidergic neurons, but their potential role in regulating microglial function is largely unknown. Here, we aimed to investigate the effect of the OR agonists DAMGO, DADLE and U-50488 on the polarization of C8-B4 microglial cells. We observed that opioids suppressed lipopolysaccharide (LPS)-triggered M1 polarization and promoted M2 polarization. This was reflected in lower phagocytic activity, lower production of NO, lower expression of TNF-α, IL-1β, IL-6, IL-86 and IL-12 beta p40 together with higher migration rate, and increased expression of IL-4, IL-10, arginase 1 and CD 206 in microglia, compared to cells affected by LPS. We demonstrated that the effect of opioids on microglial polarization is mediated by the TREM2/NF-κB signaling pathway. These results provide new insights into the anti-inflammatory and neuroprotective effects of opioids and highlight their potential in combating neurodegenerative diseases.

• MeSH
• antiflogistika farmakologie   terapeutické užití   MeSH
• lidé MeSH
• lipopolysacharidy * farmakologie   MeSH
• mikroglie * metabolismus   MeSH
• opioidní analgetika metabolismus   farmakologie   terapeutické užití   MeSH
• receptory opiátové metabolismus   terapeutické užití   MeSH
• zánět farmakoterapie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Pulmonary arterial hypertension (PAH) isa fatal disease characterized by vascular remodeling and chronic inflammation. Macrophages are the key orchestrators of inflammatory and repair responses, and have been demonstrated to be vital in the pathogenesis of PAH. However, specific phenotype of macrophage polarization (M1 & M2 macrophage) in the development of PAH and the underlying mechanisms how they work are still largely unclear. A rat model of monocrotaline (MCT) induced PAH was used. Hemodynamic analysis and histopathological experiments were conducted at day 3, 7, 14, 21 and 28, respectively. In PAH rat lung tissue, confocal microscopic images showed that CD68+NOS2+ M1-like macrophages were remarkably infiltrated on early stage, but dramatically decreased in mid-late stage. Meanwhile, CD68+CD206+ M2-like macrophages in lung tissue accumulated gradually since day 7 to day 28, and the relative ratio of M2/M1 macrophage increased over time. Results detected by western blot and immunohistochemistry were consistent. Further vitro functional studies revealed the possible mechanism involved in this pathophysiological process. By using Transwell co-culture system, it was found that M1 macrophages inducedendothelial cellapoptosis, while M2 macrophages significantly promoted proliferation of both endothelial cell and smooth muscle cell.These data preliminarily demonstrated a temporal dynamic change of macrophage M1/M2 polarization status in the development of experimental PAH. M1 macrophages participated in the initial stage of inflammation by accelerating apoptosis of endothelial cell, while M2 macrophages predominated in the reparative stage of inflammation and the followed stage of aberrant tissue remodeling.

• MeSH
• antigeny diferenciační myelomonocytární metabolismus   MeSH
• apoptóza MeSH
• arteria pulmonalis metabolismus   patologie   MeSH
• časové faktory MeSH
• CD antigeny metabolismus   MeSH
• cytokiny metabolismus   MeSH
• endoteliální buňky pupečníkové žíly (lidské) metabolismus   patologie   MeSH
• fenotyp MeSH
• kokultivační techniky MeSH
• kultivované buňky MeSH
• lidé MeSH
• makrofágy metabolismus   patologie   MeSH
• mediátory zánětu metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• monokrotalin MeSH
• myocyty hladké svaloviny metabolismus   patologie   MeSH
• plicní arteriální hypertenze chemicky indukované   metabolismus   patologie   MeSH
• potkani Sprague-Dawley MeSH
• proliferace buněk MeSH
• receptor mannózy metabolismus   MeSH
• remodelace cév * MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Within the last decade, macrophages have been shown to be capable of differentiating toward a classically activated phenotype (M1) with a high antimicrobial potential or an alternatively activated phenotype (M2). Some pathogens are capable of interfering with differentiation in order to down-regulate the anti-microbial activity and enhance their survival in the host. RESULTS: To test this ability in Salmonella enterica serovar Typhimurium, we infected porcine alveolar macrophages with wild-type Salmonella Typhimurium and its isogenic mutants devoid of two major pathogenicity islands, SPI-1 and SPI-2. The induction of genes linked with M1 or M2 polarization was determined by quantification of gene expression by RT-qPCR. The ΔSPI-1 mutant induced a high, dose-dependent M1 response but a low M2 response in infected macrophages. On the other hand, wild-type Salmonella Typhimurium induced a low M1 response but a high, dose-dependent M2 response in infected macrophages. The response to ΔSPI-2 mutant infection was virtually the same as the wild-type strain. CONCLUSIONS: We therefore propose that Salmonella Typhimurium DT104 studied here can polarize macrophages towards the less bactericidal M2 phenotype and that this polarization is dependent on the type III secretion system encoded by SPI-1.

• MeSH
• alveolární makrofágy cytologie   fyziologie   MeSH
• bakteriální proteiny genetika   metabolismus   MeSH
• cytokiny metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• prasata MeSH
• regulace genové exprese u bakterií fyziologie   MeSH
• Salmonella typhimurium genetika   metabolismus   MeSH
• signální transdukce MeSH
• transkriptom MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Macrophages derive from human embryonic and fetal stem cells and from human bone marrow-derived blood monocytes. They play a major homeostatic role in tissue remodeling and maintenance facilitated by apoptotic "eat me" opsonins like CRP, serum amyloid P, C1q, C3b, IgM, ficolin, and surfactant proteins. Three subsets of monocytes, classic, intermediate, and nonclassic, are mobilized and transmigrate to tissues. Implant-derived wear particles opsonized by danger signals regulate macrophage priming, polarization (M1, M2, M17, and Mreg), and activation. CD14(+) monocytes in healthy controls and CD16(+) monocytes in inflammation differentiate/polarize to foreign body giant cells/osteoclasts or inflammatory dendritic cells (infDC). These danger signal opsonins can be pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs), but in aseptic loosening, usually are damage-associated molecular patterns (DAMPs). Danger signal-opsonized particles elicit "particle disease" and aseptic loosening. They provide soluble and cell membrane-bound co-stimulatory signals that can lead to cell-mediated immune reactions to metal ions. Metal-on-metal implant failure has disclosed that quite like Ni(2+), its neighbor in the periodic table Co(2+) can directly activate toll-like receptor 4 (TLR4) as a lipopolysaccharide-mimic. "Ion disease" concept needs to be incorporated into the "particle disease" concept, due to the toxic, immune, and inflammatory potential of metal ions.

• MeSH
• aktivace makrofágů MeSH
• artroplastiky kloubů MeSH
• buněčná diferenciace MeSH
• lidé MeSH
• makrofágy imunologie   metabolismus   MeSH
• polarita buněk MeSH
• protézy kloubů škodlivé účinky   MeSH
• selhání protézy * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Inhalation of nanomaterials may induce inflammation in the lung which if left unresolved can manifest in pulmonary fibrosis. In these processes, alveolar macrophages have an essential role and timely modulation of the macrophage phenotype is imperative in the onset and resolution of inflammatory responses. This study aimed to investigate, the immunomodulating properties of two industrially relevant high aspect ratio nanomaterials, namely nanocellulose and multiwalled carbon nanotubes (MWCNT), in an alveolar macrophage model. METHODS: MH-S alveolar macrophages were exposed at air-liquid interface to cellulose nanocrystals (CNC), cellulose nanofibers (CNF) and two MWCNT (NM-400 and NM-401). Following exposure, changes in macrophage polarization markers and secretion of inflammatory cytokines were analyzed. Furthermore, the potential contribution of epigenetic regulation in nanomaterial-induced macrophage polarization was investigated by assessing changes in epigenetic regulatory enzymes, miRNAs, and rRNA modifications. RESULTS: Our data illustrate that the investigated nanomaterials trigger phenotypic changes in alveolar macrophages, where CNF exposure leads to enhanced M1 phenotype and MWCNT promotes M2 phenotype. Furthermore, MWCNT exposure induced more prominent epigenetic regulatory events with changes in the expression of histone modification and DNA methylation enzymes as well as in miRNA transcript levels. MWCNT-enhanced changes in the macrophage phenotype were correlated with prominent downregulation of the histone methyltransferases Kmt2a and Smyd5 and histone deacetylases Hdac4, Hdac9 and Sirt1 indicating that both histone methylation and acetylation events may be critical in the Th2 responses to MWCNT. Furthermore, MWCNT as well as CNF exposure led to altered miRNA levels, where miR-155-5p, miR-16-1-3p, miR-25-3p, and miR-27a-5p were significantly regulated by both materials. PANTHER pathway analysis of the identified miRNA targets showed that both materials affected growth factor (PDGF, EGF and FGF), Ras/MAPKs, CCKR, GnRH-R, integrin, and endothelin signaling pathways. These pathways are important in inflammation or in the activation, polarization, migration, and regulation of phagocytic capacity of macrophages. In addition, pathways involved in interleukin, WNT and TGFB signaling were highly enriched following MWCNT exposure. CONCLUSION: Together, these data support the importance of macrophage phenotypic changes in the onset and resolution of inflammation and identify epigenetic patterns in macrophages which may be critical in nanomaterial-induced inflammation and fibrosis.

• MeSH
• celulosa metabolismus   MeSH
• epigeneze genetická MeSH
• lidé MeSH
• makrofágy metabolismus   MeSH
• mikro RNA * genetika   metabolismus   MeSH
• nanotrubičky uhlíkové * toxicita   chemie   MeSH
• zánět metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

This mini-review summarizes the current evidence for the role of macrophage activation and polarization in inflammation and immune response pertinent to interstitial lung disease, specifically pulmonary fibrosis. In the fibrosing lung, the production and function of inflammatory and fibrogenic mediators involved in the disease development have been reported to be regulated by the effects of polarized M1/M2 macrophage populations. The M1 and M2 macrophage phenotypes were suggested to correspond with the pro-inflammatory and pro-fibrogenic signatures, respectively. These responses towards tissue injury followed by the development and progression of lung fibrosis are further regulated by macrophage-derived microRNAs (miRNAs). Besides cellular miRNAs, extracellular exosomal-miRNAs derived from M2 macrophages have also been proposed to promote the progression of pulmonary fibrosis. In a future perspective, harnessing the noncoding miRNAs with a key role in the macrophage polarization is, therefore, suggested as a promising therapeutic strategy for this debilitating disease.

• MeSH
• aktivace makrofágů genetika   imunologie   MeSH
• biologické markery MeSH
• biologické modely MeSH
• cytokiny metabolismus   MeSH
• exozómy metabolismus   MeSH
• lidé MeSH
• makrofágy imunologie   metabolismus   MeSH
• mediátory zánětu metabolismus   MeSH
• mikro RNA genetika   MeSH
• náchylnost k nemoci * MeSH
• plasticita buňky MeSH
• plicní fibróza etiologie   metabolismus   patologie   MeSH
• regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH