[Cellular and molecular mechanisms of inflammation of esophageal mucosa under different clinical course of gastroesophageal reflux disease and its complications].

The review presents modern data on the cellular and molecular mechanisms of inflammatory changes of esophageal mucosa exposed to different types of reluctate (gastric, biliary or duodenal/mixed). The authors describe data on key mediators of inflammation in gastroesophageal reflux disease (GERD) and their major cellular sources, changes of the immune profile of patients. Discusses the possible impact of changes in the cellular and molecular components in the development of the inflammatory response in the esophagus on the clinical features of GERD and its therapy-refractory forms.

Features of the functional activity of macrophage link of immunity with gastroesophageal reflux disease depending on the type of reluctate: in vitro model.

AIM: A generalized analysis of changes in functional activity of macrophages on the basis of phagocytic activity, cytokine profile, changes in the level of expression of surface markers characteristic of pro- or anti-inflammatory phenotype of the cells when exposed to reluctate. MATERIALS AND METHODS: Developed in vitro model of co-peritoneal macrophages of mice With57/BL6 (n=65) and reluctate patients with gastroesophageal reflux disease (GERD; n=65) having different pH values (three group comparison). Took into account the standard criteria phagocytic ability (absorption Staphylococcus aureus 9198, light microscopy), secretory activity (cytokine profile Th1/Th2, flow cytometry) and receptor characterization of macrophages (expression of CD25/80/163/206, flow cytometry). RESULTS: The phagocytic activity of macrophages, calculated on the basis of the average number of bacteria ingested by one phagocyte, is not associated with the pH value of the added reluctate. It is established that the alkalinisation of reluctate leads to significant alteration in the expression of CD receptors - decrease M1 and increase M2. The index of total production of Th1/Тһ2 in groups progressively decreased with increasing pH of reluctate and amounted to 3.6 units in the group pH from 4.6 to 6.6; 2.8 units group a pH of 6.7-7.2 and 1.6 units in the group pH of 7.3 to 8.1, due to increased production of Th2 cytokines at offset reluctate pH to slightly alkaline side. The data obtained indicate the increase of expression and secretion of anti-inflammatory markers at an alkaline pH shift of reluctate. Analysis of the studied characteristics of the activity profile of macrophages in the proposed in vitro model justifies the need for considering the peculiarities of the functional activity of macrophages under the influence of reluctate different nature. The special importance of studying the cytokine profile and characteristics of the functional activity of macrophages in patients with GERD, given the nature of reluctate.

Cellular and molecular mechanisms of inflammation of esophageal mucosa under different.

The review presents modern data on the cellular and molecular mechanisms of inflammatory changes of esophageal mucosa exposed to different types of reluctate (gastric, biliary or duodenal/mixed). The authors describe data on key mediators of inflammation in gastroesophageal reflux disease (GERD) and their major cellular sources, changes of the immune profile of patients. Discusses the possible impact of changes in the cellular and molecular components in the development of the inflammatory response in the esophagus on the clinical features of GERD and its therapy-refractory forms.

[Reprogrammed M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 extends lifespan of mice with experimental carcinoma].

Objective. Reprogramming of M1 macrophage phenotype with inhibited M2 phenotype transcription factors, such as STAT3, STAT6 and SMAD and assess their impact on the development of Ehrlich carcinoma (EC) in vitro and in vivo. Methods. Tumor growth in vitro was initiated by addition of EC cells in RPMI-1640 culture medium and in vivo by intraperitoneal of EC cell injection into mice. Results. It was found that M1-STAT3/6- SMAD3 macrophages have a pronounced anti-tumor effect in vitro, and in vivo, which was greater than anti-tumor effects of M1, M1-STAT 3/6, M1-SMAD3 macrophages and cisplatin. Conclusion. M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 effectively restrict tumor growth. The findings justify the development of new anti-tumor cell therapy technology.

Effects of Phenotype of Retinal Macrophages on the Features of Angiogenesis of Murine Retina.

The period of forming of superficial vascular plexus during physiological retinal angiogenesis was shorter in C57Bl/6 mice. Experiments on the model of oxygen-induced retinopathy showed that avascular and vascularized zones in BALB/c mice on day 17 are smaller than in C57Bl/6 mice are by 5 and 1.5 times, respectively. The obtained results confirmed the importance of phenotype of retinal macrophages in the regulation of processes of both physiological and pathological retinal angiogenesis.

[Genetic features of nitric oxide generating systems predetermine the body's resistance to the development of carcinoma].

Predisposition to tumors is often determined by how effectively the genotype of an individual forms an immune defense. An important factor of such protection is macrophage NO. We assumed that the body's vulnerability to the development of tumors may depend from the characteristics of the NO generating systems. The content of NO in the tumor changed by ITU, inhibitor of iNOS, c-PTIO, traps and SNP, donor NO. Production of macrophage NO were evaluated by nitrites in the culture media. iNOS was assessed using the Western blot analysis. Phenotype of macrophages was assessed using cytometry for CD labels. Life span of mice C57BL/6N with Ehrlich tumor was 25% greater than that of the C57BL/6J. Reducing the content of NO in the tumor reduced life expectancy of high-resistance to tumor subline C57BL/6N at 23%. Increase of NO increased life expectancy of low-resistance subline C57BL/6J at 26%. Macrophages of C57BL/6N were 1.5 times higher contents of iNOS and NO production, as compared with macrophages of C57BL/6J. CD phenotype markers determined the macrophage phenotype C57BL/6N as M1 and C57BL/6J mice macrophage phenotype as M2. Thus, the body's vulnerability to the development of tumors may depend from the characteristics of the NO generating systems. C57BL/6J, unlike C57BL/6N does not synthesize NNT (nicotinamide nucleotide transhydrogenase) and have differences in the single nucleotide polymorphism (SNP). The important role of NO in the resistance to Carcinoma, NNT and SNP deserve attention in the development of new methods of antitumor therapy.

[An immune response and an alveolar macrophage phenotype in asthma, gastroesophageal reflux disease and their concurrence].

AIM: To test the hypothesis that an impaired pulmonary immune response in asthma, gastroesophageal reflux disease (GERD) and their concurrence of these diseases is largely determined by disordered alveolar macrophage (AM) reprogramming and to assess the pulmonary immune response and an AM phenotype in patients with asthma, GERD and their concurrence. SUBJECTS AND METHODS: The levels of proinflammatory M1 cytokines, such as IL-1ß, IL-8, IL-12p70, IFN-γ, TNF-α, and TNF-ß, anti-inflammatory M2 cytokines, such as IL-4, IL-5, and IL-10, and bivalent M1/M2 cytokines, such as IL-2 and IL-6, were determined in bronchoalveolar lavage fluid (BALF) and AM culture medium. RESULTS: Serious deformations in the pulmonary immune response were first detected in patients with mixed pathology towards to an anti-inflammatory M2 phenotype. The change in the pulmonary immune response phenotype in GERD towards Ml and in comorbidity towards M2 was coincident with that of the AM phenotype. In asthma, the change in the pulmonary immune response phenotype occurred towards to M2 and that in the intrinsic AM phenotype did towards M1. This phenotype is likely to form a proinflammatory component and to cause an asthma exacerbation. CONCLUSION: Analysis of the spectrum of cytokines in BALF and produced by macrophages in asthma, GERD and their concurrence validated the hypothesis that impaired pulmonary immune responses in these diseases are associated with disordered AM reprogramming. The findings also suggest that therapy for the inflammatory component in these diseases should be performed by taking into account the specificity of the cytokine structure of an immune response and the phenotypic heterogeneity of immune cells.

Alternative reprogramming of M1/M2 phenotype of mouse peritoneal macrophages in vitro with interferon-γ and interleukin-4.

An important role in the development of the immune response is played by macrophages that acquire either anti-inflammatory M1 or anti-inflammatory M2 phenotype depending on their microenvironment. The possibility of targeted reprogramming of the initial M2 macrophage phenotype towards M1 phenotype and vice versa using macrophage reprogramming factors IFN-γ and IL-4, respectively, was demonstrated. We showed that macrophages of genetically different mouse strains did not practically differ by their reprogramming capacity. Our findings suggest that macrophage programming not only participates in the triggering of the immune response, but also can ensure plasticity of functional activity during the developing response.