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.

• Klíčová slova
• M1/M2, cancer, differentiation, infection, macrophages, polarisation,
• 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
• Názvy látek
• cytokiny * MeSH

Macrophages are a specific group of cells found in all body tissues. They have specific characteristics in each of the tissues that correspond to the functional needs of the specific environment. These cells are involved in a wide range of processes, both pro-inflammatory and anti-inflammatory ("wound healing"). This is due to their specific capacity for so-called polarization, a phenotypic change that is, moreover, partially reversible compared to other differentiated cells of the human body. This promises a wide range of possibilities for its influence and thus therapeutic use. In this article, we therefore review the mechanisms that cause polarization, the basic classification of polarized macrophages, their characteristic markers and the effects that accompany these phenotypic changes. Since the study of pulmonary (and among them mainly alveolar) macrophages is currently the focus of scientific interest of many researchers and these macrophages are found in very specific environments, given mainly by the extremely high partial pressure of oxygen compared to other locations, which specifically affects their behavior, we will focus our review on this group.

• MeSH
• antiflogistika * farmakologie   MeSH
• buněčná diferenciace fyziologie   MeSH
• lidé MeSH
• makrofágy * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antiflogistika * MeSH

Accumulation of visceral adipose tissue correlates with elevated inflammation and increased risk of metabolic diseases. However, little is known about the molecular mechanisms that control its pathological expansion. Transcription factor interferon regulatory factor 5 (IRF5) has been implicated in polarizing macrophages towards an inflammatory phenotype. Here we demonstrate that mice lacking Irf5, when placed on a high-fat diet, show no difference in the growth of their epididymal white adipose tissue (epiWAT) but they show expansion of their subcutaneous white adipose tissue, as compared to wild-type (WT) mice on the same diet. EpiWAT from Irf5-deficient mice is marked by accumulation of alternatively activated macrophages, higher collagen deposition that restricts adipocyte size, and enhanced insulin sensitivity compared to epiWAT from WT mice. In obese individuals, IRF5 expression is negatively associated with insulin sensitivity and collagen deposition in visceral adipose tissue. Genome-wide analysis of gene expression in adipose tissue macrophages highlights the transforming growth factor β1 (TGFB1) gene itself as a direct target of IRF5-mediated inhibition. This study uncovers a new function for IRF5 in controlling the relative mass of different adipose tissue depots and thus insulin sensitivity in obesity, and it suggests that inhibition of IRF5 may promote a healthy metabolic state during this condition.

• MeSH
• bílá tuková tkáň metabolismus   MeSH
• dieta s vysokým obsahem tuků MeSH
• interferonové regulační faktory genetika   MeSH
• inzulinová rezistence genetika   MeSH
• lidé MeSH
• makrofágy MeSH
• myši MeSH
• obezita farmakoterapie   genetika   patologie   MeSH
• regulace genové exprese MeSH
• transformující růstový faktor beta1 biosyntéza   MeSH
• zánět farmakoterapie   genetika   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interferonové regulační faktory MeSH
• Irf5 protein, mouse MeSH Prohlížeč
• Tgfb1 protein, mouse MeSH Prohlížeč
• transformující růstový faktor beta1 MeSH

Interferon (IFN) signaling has been suggested to play an important role in colorectal carcinogenesis. Our study aimed to examine potentially functional genetic variants in interferon regulatory factor 3 (IRF3), IRF5, IRF7, type I and type II IFN and their receptor genes with respect to colorectal cancer (CRC) risk and clinical outcome. Altogether 74 single nucleotide polymorphisms (SNPs) were covered by the 34 SNPs genotyped in a hospital-based case-control study of 1327 CRC cases and 758 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall survival and event-free survival in a subgroup of 483 patients. Seven SNPs in IFNA1, IFNA13, IFNA21, IFNK, IFNAR1 and IFNGR1 were associated with CRC risk. After multiple testing correction, the associations with the SNPs rs2856968 (IFNAR1) and rs2234711 (IFNGR1) remained formally significant (P = 0.0015 and P<0.0001, respectively). Multivariable survival analyses showed that the SNP rs6475526 (IFNA7/IFNA14) was associated with overall survival of the patients (P = 0.041 and event-free survival among patients without distant metastasis at the time of diagnosis, P = 0.034). The hazard ratios (HRs) for rs6475526 remained statistically significant even after adjustment for age, gender, grade and stage (P = 0.029 and P = 0.036, respectively), suggesting that rs6475526 is an independent prognostic marker for CRC. Our data suggest that genetic variation in the IFN signaling pathway genes may play a role in the etiology and survival of CRC and further studies are warranted.

• MeSH
• genetická predispozice k nemoci * MeSH
• genotyp MeSH
• interferony genetika   metabolismus   MeSH
• jednonukleotidový polymorfismus * MeSH
• kolorektální nádory genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• multivariační analýza MeSH
• nemocnice MeSH
• přežití bez známek nemoci MeSH
• proporcionální rizikové modely MeSH
• rizikové faktory MeSH
• senioři MeSH
• signální transdukce MeSH
• studie případů a kontrol MeSH
• vazebná nerovnováha MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interferony MeSH

Transplantation of mesenchymal stem cells (MSC) improves functional recovery in experimental models of spinal cord injury (SCI); however, the mechanisms underlying this effect are not completely understood. We investigated the effect of intrathecal implantation of human MSC on functional recovery, astrogliosis and levels of inflammatory cytokines in rats using balloon-induced spinal cord compression lesions. Transplanted cells did not survive at the lesion site of the spinal cord; however, functional recovery was enhanced in the MSC-treated group as was confirmed by the Basso, Beattie, and Bresnahan (BBB) and the flat beam test. Morphometric analysis showed a significantly higher amount of remaining white matter in the cranial part of the lesioned spinal cords. Immunohistochemical analysis of the lesions indicated the rearrangement of the glial scar in MSC-treated animals. Real-time PCR analysis revealed an increased expression of Irf5, Mrc1, Fgf2, Gap43 and Gfap. Transplantation of MSCs into a lesioned spinal cord reduced TNFα, IL-4, IL-1β, IL-2, IL-6 and IL-12 and increased the levels of MIP-1α and RANTES when compared to saline-treated controls. Intrathecal implantation of MSCs reduces the inflammatory reaction and apoptosis, improves functional recovery and modulates glial scar formation after SCI, regardless of cell survival. Therefore, repeated applications may prolong the beneficial effects induced by MSC application.

• MeSH
• chemokin CCL5 genetika   metabolismus   MeSH
• fibroblastový růstový faktor 2 genetika   metabolismus   MeSH
• gliový fibrilární kyselý protein genetika   metabolismus   MeSH
• interferonové regulační faktory genetika   metabolismus   MeSH
• interleukiny genetika   metabolismus   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• lokomoce MeSH
• mezenchymální kmenové buňky metabolismus   MeSH
• poranění míchy metabolismus   terapie   MeSH
• potkani Wistar MeSH
• protein GAP-43 genetika   metabolismus   MeSH
• receptory imunologické genetika   metabolismus   MeSH
• TNF-alfa genetika   metabolismus   MeSH
• transplantace mezenchymálních kmenových buněk * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemokin CCL5 MeSH
• fibroblastový růstový faktor 2 MeSH
• gliový fibrilární kyselý protein MeSH
• interferonové regulační faktory MeSH
• interleukiny MeSH
• protein GAP-43 MeSH
• receptory imunologické MeSH
• TNF-alfa MeSH