The important component of obesity pathogenesis is inflammatory activation of innate immune cells within adipose tissue and in other body locations. Both the course of obesity and innate immune reactivity are characterized by sex-associated differences. The aim of the work was a comparative investigation of metabolic profiles of phagocytes from different locations in male and female rats with MSG-induced obesity. The administration of monosodium glutamate (MSG) caused obesity, with sex-associated differences, that was more severe in male rats. Obesity was associated with pro-inflammatory activation of CD14+ phagocytes from adipose tissue in female, but not in male rats, which was demonstrated by decreased phagocytosis activity along with increased ROS generation. Phagocytes from the peritoneal cavity and peripheral blood of obese female rats exhibited neutral metabolic profile, whereas those cells from obese male rats displayed a pro-inflammatory metabolic profile. Thus, the manifestation of obesity-induced inflammation was characterized by different patterns of metabolic profile of phagocytes in male and female rats. Identified immune cell characteristics expand our knowledge of obesity immunobiology and may help to develop more effective preventive and therapeutic interventions for obese patients of different sexes.
NSC 631570 causes M1 (N1) shift of phagocytes after in vivo introduction. Moderate physical exercise exerts a negative effect on the immunomodulatory action of NSC 631570 by abrogating M1 (N1) shift of circulating phagocytes. One of the reasons for such an effect could be an increase in PPAR-γ expression by phagocytes.
Мета. Дослідити вплив лікування хворих з гострим панкреатитом (ГП) з використанням препарату улінастатин (УС) на функціональний стан циркулюючих лейкоцитів та сироватковий рівень негістонових білків 1 високомобільної групи (High Mobility Group Box 1 protein - HMGB1).
Матеріали і методи. У дослідження включено 60 хворих з ГП, яких лікували у хірургічному відділенні №2 Київської міської клінічної лікарні швидкої медичної допомоги. Про стан метаболізму циркулюючих фагоцитів судили за показниками продукції реактивних форм кисню (РФК) та фагоцитарною активністю, які визначали методом проточної цитометрії. Для визначення сироваткового рівня HMGB1 застосовували метод імуноферментного аналізу.
Результати. Про позитивний терапевтичний ефект УС свідчили зниження синтезу РФК циркулюючими лейкоцитами (в середньому у 2 рази), помірне посилення фагоцитарної активності циркулюючих моно- та поліморфноядерних фагоцитів, зниження сироваткового рівня HMGB1 на 27%.
Висновки. Включення до складу лікувального алгоритму УС посилює протизапальний та антиоксидантний ефекти лікування хворих з ГП.
Objectives: NSC631570 is a cytotoxic drug with the ability to be selectively accumulated in tumor tissue and activate apoptosis only in malignant cells and not in normal cells. Therapy with NSC631570 is accompanied by the stimulation of anticancer immune responses. It is known that cytotoxic anticancer drugs have additional effects on the immune system of tumor-bearing organism by increasing the immunogenic properties of tumor cells. This study aimed to investigate the immunogenicity of melanoma B16 after treatment with NSC631570. Methods: Two melanoma B16 sublines with different metastatic potentials were used. For in vivo growth cells were inoculated intravenously into C57BL/6 mice. The anticancer effect was calculated according to the growth inhibition index. Cell viability was determined by the MTT test. Cell apoptosis and necrosis were assessed by flow cytometry. HMGB1 expression, the serum level of cytokines and cytokine profile in tumor tissue were determined by ELISA. TAP1 and TAP2 expression was evaluated in RT-PCR and by Western blot. Results: Treatment of melanoma B16 cells with NSC631570 at apoptogenic concentrations induced tumor cell death accompanied by dose-dependent HMGB1 release in vitro. At the nonapoptogenic concentration the preparation caused an increase in TAP expression. The therapeutic efficacy of NSC631570 was also associated with strong release of HMGB1 in the serum of tumor-bearing mice and was more expressed in the case of the high-metastatic tumor variant. The therapeutic effect was accompanied by an increase of levels of Th1 cytokines in the serum and in tumor tissue of treated animals. Conclusion: In addition to the direct induction of tumor cell apoptosis, the preparation can increase the tumor immunogenicity.
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