Bone marrow-derived macrophages exclusively expressed caveolin-2: The role of inflammatory activators and hypoxia

Michaela, Maceckova; Martišková, Hana; Koudelka, Adolf; Kubala, Lukáš; Lojek, Antonı́n; Pekarová, Michaela

doi:10.1016/j.imbio.2015.06.018

Cited by 12 publications

(8 citation statements)

References 74 publications

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“…A substantial amount of NO in tumors is produced from iNOS strongly expressed in macrophages [30] . It was shown that, in unstimulated macrophages, hypoxia had only a negligible effect on iNOS expression [31] , whereas acidosis reduced iNOS in M2 macrophages [15] . For this reason, the observed iNOS reduction in vivo may be attributable to acidosis-induced changes in the macrophage population.…”

Section: Discussionmentioning

confidence: 99%

Tumor Acidosis and Hypoxia Differently Modulate the Inflammatory Program: Measurements In Vitro and In Vivo

2017

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Inflammatory mediators produced by the tumor cells are of importance for immune response but also for malignant progression. The aim of the study was to analyze the expression of monocyte chemoattractant protein-1, interleukin-6 (IL-6), tumor necrosis factor-α, inducible isoform of nitric oxide synthase (iNOS), cyclooxygenase-2, and osteopontin in vitro in two different tumor cell lines under hypoxia (pO2 ≈ 1.5 mmHg) and/or acidosis (pH = 6.6) for up to 24 hours since hypoxia and acidosis are common characteristics of solid tumors. Additionally, the same tumor cell lines implanted in vivo were made hypoxic and acidotic artificially for 24 hours, after which the cytokine expression was measured. Finally, the activation of ERK1/2 and p38 by acidosis/hypoxia and their impact on cytokine expression were studied. The results indicate that acidosis and hypoxia have fundamentally different (often opposing) effects on cytokine expression. In addition, these effects were tumor cell line specific. When combining hypoxia and acidosis, the overall changes reflect an additive effect of both conditions alone, indicating that hypoxia and acidosis act by independent mechanisms. The in vivo changes corresponded well with the results obtained in the isolated tumor cells. Only iNOS expression was downregulated in vivo but increased in cell culture. For IL-6 expression, the acidosis-induced changes were dependent on ERK1/2 activation. In conclusion, it was demonstrated that the environmental pO2 and pH strongly affect the expression of inflammatory mediators in tumor cells. In vivo, most of the inflammatory mediators were downregulated, which could limit the activation of immune cells and by this foster the immune escape of tumors.

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Section: Discussionmentioning

confidence: 99%

Tumor Acidosis and Hypoxia Differently Modulate the Inflammatory Program: Measurements In Vitro and In Vivo

2017

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“…Caveolin-2 (Cav-2), from the same protein family, is expressed in isolated murine bone marrow-derived macrophages under resting and inflammatory conditions (Maceckova et al, 2015). Cav-2 interacts with Cav-1 in many cells, and Caveolin-3 (Cav-3) is primarily localized in muscle tissues (Way & Parton, 1995).…”

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confidence: 99%

Expression of caveolin‐1 in the interfollicular but not the follicle‐associated epithelial cells in the bursa of fabricius of chickens

Bódi

Minkó

Fölker

et al. 2017

Journal of Morphology

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The surface epithelium of the bursa of Fabricius consists of interfollicular (IFE) and follicleassociated epithelium (FAE). The IFE comprises (i) cylindrical-shaped secretory cells (SC) and (ii) cuboidal basal cells (BCs). The FAE provides histological and two-way functional connections between the bursal lumen and medulla of the follicle. We used a carbon solution and anticaveolin-1 (Cav-1) to study the endocytic activity of FAE. Carbon particles entered the intercellular space of FAE, but the carbon particles were not internalized by the FAE cells.

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“…Native BMCs were isolated from healthy C57BL/6J mice (males, 25–30 g, 12–14 weeks old; Masaryk University, Brno, Czech Republic) by flushing femora and tibiae [41]. The experiments were approved by the Animal Care Committee and were in accordance with the EU and NIH Guide for Care and Use of Laboratory Animals.…”

Section: Methodsmentioning

confidence: 99%

Nitro-oleic acid regulates growth factor-induced differentiation of bone marrow-derived macrophages

Verescakova

Ambrožová

Kubala

et al. 2017

Free Radical Biology and Medicine

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Many diseases accompanied by chronic inflammation are connected with dysregulated activation of macrophage subpopulations. Recently, we reported that nitro-fatty acids (NO2-FAs), products of metabolic and inflammatory reactions of nitric oxide and nitrite, modulate macrophage and other immune cell functions. Bone marrow cell suspensions were isolated from mice and supplemented with macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with NO2-OA for different times. RAW 264.7 macrophages were used for short-term (1–5 min) experiments. We discovered that NO2-OA reduces cell numbers, cell colony formation, and proliferation of macrophages differentiated with colony-stimulating factors (CSFs), all in the absence of toxicity. In a case of GM-CSF-induced bone marrow-derived macrophages (BMMs), NO2-OA acts via downregulation of signal transducer and activator of transcription 5 (STAT5) and extracellular signal-regulated kinase (ERK) activation. In the case of M-CSF-induced BMMs, NO2-OA decreases activation of M-CSFR and activation of related PI3K and ERK. Additionally, NO2-OA also attenuates activation of BMMs. In aggregate, we demonstrate that NO2-OA regulates the process of macrophage differentiation and that NO2-FAs represent a promising therapeutic tool in the treatment of inflammatory pathologies linked with increased accumulation of macrophages in inflamed tissues.

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Bone marrow-derived macrophages exclusively expressed caveolin-2: The role of inflammatory activators and hypoxia

Cited by 12 publications

References 74 publications

Tumor Acidosis and Hypoxia Differently Modulate the Inflammatory Program: Measurements In Vitro and In Vivo

Tumor Acidosis and Hypoxia Differently Modulate the Inflammatory Program: Measurements In Vitro and In Vivo

Expression of caveolin‐1 in the interfollicular but not the follicle‐associated epithelial cells in the bursa of fabricius of chickens

Nitro-oleic acid regulates growth factor-induced differentiation of bone marrow-derived macrophages

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