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• The current study was planned to evaluate the effect of dexamethasone treated monocytes, which carry antigens, on the immune system responses. • Treatment of macrophage with 10-5 M of dexamethasone for 48 h increased the IL-10 and TGF-β and reduced TNF-α and IL-1 gene expressions. • The highest antigens were determined in treated macrophages five days after treatment. • The effects of dexamethasone on metabolism and differentiation of monocytes was depended on the dose, time, and duration of the treatment. The characteristics of M2 macrophages suggest immunotherapeutic approaches for inducing immunological tolerance. The current study aimed to evaluate the effect of Dexamethasone (Dex) treatment on monocytes polarization and its impact on immune responses. The monocytes were extracted from the rat's blood samples. The effects of Dex concentration and treatment duration on monocyte viability, phagocytosis of rabbit red blood cell (RRBC) antigens, and cytokine gene expression were evaluated using MTT, ELISA, and Real-Time PCR analysis, respectively. The monocytes treated with Dex were injected into the rats as an autograft. The effects of the grafted cells were assessed on immune responses, monocyte differentiation, and pathological lesions, in comparison to the control groups. Treatment of monocytes with 10-5 M of Dex for 48 h increased the expression of IL-10 and TGF-β genes, while reducing the expression of TNF-α and IL-1 genes. The monocytes treated with antigen and Dex showed higher CD206 gene expression compared to CD80. The cells that were treated with Dex had the highest concentration of antigens after five days. Administration of the grafted cells to the animals has some significant effects on innate immune responses and no impact on pathological lesions. The group that received cells treated with Dex and antigen experienced a significant decrease in anti-RBC antibody titers. Additionally, there was a significant difference in the expression of cytokine genes and M2 differentiation markers among the groups that were evaluated. The effects of Dex on the viability and differentiation of monocytes depend on the dosage, timing, and duration of the treatment. [ABSTRACT FROM AUTHOR]

Abstract Macrophages, as crucial cellular components of innate immunity, are characterized by possessing high plasticity and an abnormal ability to differentiate in response to numerous stimuli. Given this, macrophages show extreme heterogeneity under both physiological and pathological conditions. Typically, macrophages can be polarized into classically activated macrophages (M1) and alternatively activated macrophages (M2) depending on their environment. The relative functions of these two subtypes are almost exactly opposed to one another. Recent studies have suggested that some naturally occurring compounds can exert regulatory effects on the progression of macrophage polarization, which implies that they could be promising therapeutic tools to treat relevant diseases. Therefore, in our current review, we summarize recent studies on several naturally occurring compounds that may possess the ability to regulate macrophage polarization and explore the associated molecular mechanisms. Highlights • We briefly concluded the polarization of macrophages and relevant mechanisms. • We summarized several herbal compounds, which possess the regulating effects on macrophages. • We explored the molecular mechanisms of relevant compounds for the treatment of macrophage polarization. [ABSTRACT FROM AUTHOR]

Abstract Exposure to an enriched environment (EE) affects not only brain functions but also immune responses upon viral or bacterial infections. In this study, we examined changes in the phagocytic response and chemokine production of resident peritoneal macrophages after mice had been housed under EE conditions for 6 or 8 weeks, and then explored the possibility that EE could cause a change in the macrophage phenotype by means of flow cytometry as well as quantitative RT-PCR. The percentages of EE macrophages phagocytosing S. aureus and apoptotic neutrophils were significantly larger than those of standard environment (SE) macrophages. After coculturing with S. aureus , EE macrophages tended to produce greater amounts of chemokines such as MIP-2, KC and MCP-1 than SE ones, although the increases for MIP-2 and KC were not statistically significant. As compared with SE macrophages, EE macrophages included more CD40-positive cells (M1 marker), and expressed more mRNAs of IL-6 (M1 marker) and IRF4 (M2 marker), and less mRNA of CD38 (M1 marker), suggesting either the possibility that EE macrophages are a mixed population of M1 and M2 macrophages or the possibility that they are a unique population with a mixed M1 and M2 macrophage phenotype. Highlights • An enriched environment (EE) increased phagocytosis of S. aureus by macrophages. • EE increased phagocytosis of apoptotic neutrophils by macrophages. • EE tended to increase S. aureus -induced chemokine production by macrophages. • EE macrophages showed a mixed M1 and M2 macrophage phenotype. [ABSTRACT FROM AUTHOR]

The anti-inflammatory actions of IL-4 are well established through earlier findings. However, the exact mechanism it uses to downregulate the pro-inflammatory cytokine production through monocytes and macrophages is poorly understood. In this study, we examined the effect of IL-4 in the induction of 11β-HSD1 in the two main classes of monocytes, CD14 ++ CD16 − (CD14) and CD14 + CD16 + (CD16). Peripheral Blood Mononuclear Cells (PBMCs) were isolated from 17 healthy donors and were sorted into CD14 and CD16 subpopulations using cell sorting. Effect of IL-4 on 11β-HSD1-enzyme activity was measured in sorted and unsorted monocytes using Homogeneous Time-Resolved Fluorescence (HTRF) and M1/M2 polarization analysis was performed by flow cytometry. Our results indicate that CD14 cells are the major source of 11β-HSD1 enzyme after IL-4 stimulation and that M2 phenotype is not a pre-requisite for its synthesis. [ABSTRACT FROM AUTHOR]

• Targeting activated macrophages to suppress the pro-fibrotic phenotype is considered a potential approach for the treatment of IPF. • We found that tacrolimus is able to inhibit the pro-fibrotic phenotype (i.e., CD206, CD163,TGF-β and IL-12) of M2 macrophages. • We found that tacrolimus inhibits JAK2/STAT3 signaling by targeting JAK2 in macrophages, thereby reducing the release of various profibrotic factors secreted by M2 macrophages. • Tacrolimus inhibits M2 macrophage polarization and M2-induced FMT, thus slows down PF progression. • Our findings suggest that tacrolimus has a potential anti-fibrotic effect by modulating macrophage polarization, which may have important implications in the clinical setting. Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown cause and characterized by excessive proliferation of fibroblasts and the irregular remodeling of extracellular matrix (ECM), which ultimately cause the severe distortion of the alveolar architecture. The median survival of IPF patients is 2–5 years. IPF patients are predominantly infiltrated by M2 macrophages during the course of disease development and progression. Predominantly accumulation of M2 macrophages accelerates fibrosis progression by secreting multiple cytokines that promote fibroblast to myofibroblast transition. In the process of M2 macrophage polarization, JAK2/STAT3 signaling plays a key role, thus, targeting activated macrophages to inhibit the pro-fibrotic phenotype is considered as an approach to the potential treatment of IPF. Tacrolimus is a macrolide antibiotic that as a specific inhibitor of T -lymphocyte function and has been used widely as an immunosuppressant in human organ transplantation. In this study we explored the potential effect and mechanism of tacrolimus on pulmonary fibrosis in vivo and vitro. Here, we found that tacrolimus is capable of suppressing M2 macrophages polarization by inhibiting pro-fibrotic factors secreted by M2 macrophages. This effect further alleviates M2-induced myofibroblast activation, thus resulting in a decline of collagen deposition, pro-fibrotic cytokines secretion, recovering of lung function, ultimately relieving the progression of fibrosis in vivo. Mechanistically, we found that tacrolimus can inhibit the activation of JAK2/STAT3 signaling by targeting JAK2. Our findings indicate a potential anti-fibrotic effect of tacrolimus by regulating macrophage polarization and might be meaningful in clinical settings. [ABSTRACT FROM AUTHOR]

• Butyrate enhanced CECR1 expression in THP-1 cells. • CECR1 was involved in regulating the butyrate modulated inflammatory responses. • ADA2 positively correlated with M2 chemokines in tuberculous pleural effusion. The Cat Eye Syndrome Critical Region, Candidate 1 (CECR1) gene encoding adenosine deaminase 2 (ADA2) is mainly expressed by macrophages. Given the immunomodulatory functions of butyrate, we examined the effect of butyrate on CECR1 expression of macrophages and the relationship between ADA2 and M1/M2 macrophages-associated chemokines in pleural fluid of patients with tuberculous pleural effusion (TPE). Expression of CECR1 was evaluated in lipopolysaccharide (LPS)-stimulated and/or butyrate treated THP-1 cells. The role of CECR1 on butyrate-induced immune response was evaluated using siRNA transfected THP-1 cells. M1/M2 chemokines and ADA2 were measured in pleural fluid of patients with TPE. Butyrate promoted the expression of CECR1 and M2-macrophage markers in THP-1 cells. CECR1 was found to be involved in regulating M2 polarization in THP-1 cells treated with LPS and butyrate. Among chemokines measured in pleural fluid of patients with TPE, there was a significant negative correlation between CCL21 and ADA2 levels and between CCL25 and ADA2 levels, and a significant positive correlation between TGF-β and ADA2 levels and between IL-22 and ADA2 levels. CECR1 played an important role in the butyrate-modulated inflammatory responses in LPS-stimulated THP-1 cells. ADA2 may exert anti-inflammatory effects during the process of pleural inflammation in patients with TPE. [ABSTRACT FROM AUTHOR]