Activation of Murine Macrophages

Mosser, David M.; Gonçalves, Ricardo

doi:10.1002/0471142735.im1402s111

Cited by 29 publications

(30 citation statements)

References 36 publications

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“…AMs initially expressed higher levels of NOS-2 mRNA (*4-fold; p = 0.019) and TNF-a mRNA (*2.7-fold; p = 0.007) compared to NMs, consistent with classical activation 58 ( Supplementary Fig. S2A).…”

Section: D System To Study Effects Of Osteoarthritic Inflammationsupporting

confidence: 58%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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The goal of the present study was to develop a fully three-dimensional (3D) coculture system that would allow for systematic evaluation of the interplay between activated macrophages (AMs) and chondrocytes in osteoarthritic disease progression and treatment. Toward this end, our coculture system was first validated against existing in vitro osteoarthritis models, which have generally cultured healthy normal chondrocytes (NCs)-in two-dimensional (2D) or 3D-with proinflammatory AMs in 2D. In this work, NCs and AMs were both encapsulated within poly(ethylene glycol) diacrylate hydrogels to mimic the native 3D environments of both cell types within the osteoarthritic joint. As with previous studies, increases in matrix metalloproteinases (MMPs) and proinflammatory cytokines associated with the early stages of osteoarthritis were observed during NC-AM coculture, as were decreases in protein-level Aggrecan and collagen II. Thereafter, the coculture system was extended to osteoarthritic chondrocytes (OACs) and AMs to evaluate the potential effects of AMs on pre-existing osteoarthritic phenotypes. OACs in coculture with AMs expressed significantly higher levels of MMP-1, MMP-3, MMP-9, MMP-13, IL-1b, TNF-a, IL-6, IL-8, and IFN-g compared to OACs in mono-culture, indicating that proinflammatory macrophages may intensify the abnormal matrix degradation and cytokine secretion already associated with OACs. Likewise, AMs cocultured with OACs expressed significantly more IL-1b and VEGF-A compared to AM mono-culture controls, suggesting that OACs may intensify abnormal macrophage activation. Finally, OACs cultured in the presence of nonactivated macrophages produced lower levels of MMP-9 and proinflammatory cytokines IL-1b, TNF-a, and IFN-g compared to OACs in the OAC-AM system, results that are consistent with anti-inflammatory agents temporarily reducing certain OA symptoms. In summary, the 3D coculture system developed herein captures several key features of inflammatory OA and may prove useful in future screening of therapeutic agents and/or assessment of disease progression mechanisms.

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Section: D System To Study Effects Of Osteoarthritic Inflammationsupporting

confidence: 58%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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“…1,2 During the inflammatory response, tissue Mws are expected to sequentially develop into three different subpopulations: type-1 (Mw-1), type-2 (Mw-2) and regulatory (Reg-Mws). [3][4][5][6] During the initiation phase of inflammation, the pro-inflammatory Mw-1 subtype is generated in response to two signals (i.e., Interferon gamma (IFN-c) and tumor-necrosis factor alpha (TNF-a)) or a Toll-like receptor (TLR) ligand, such as lipopolysaccharide (LPS). During the resolution phase of inflammation, the presence of the type-2 cytokines interleukin 4 (IL-4) and IL-13 leads to the generation of anti-inflammatory Mw-2, which are associated with the coordination of tissue repair.…”

Section: Introductionmentioning

confidence: 99%

“…The third subtype (i.e., Reg-Mws) is fundamentally different from Mw-1 and Mw-2, and the generation of this subtype requires two signals. [3][4][5][6] The first signal may include IL-10, prostaglandins, immune complexes, adenine nucleotides, glucocorticoids and apoptotic cells, and the second signal is TLR activation. RegMws overproduce IL-10 but not IL-12 and exhibit potent immunosuppressive activity for modulating the acute inflammatory response and limiting tissue damage.…”

Section: Introductionmentioning

confidence: 99%

“…RegMws overproduce IL-10 but not IL-12 and exhibit potent immunosuppressive activity for modulating the acute inflammatory response and limiting tissue damage. [3][4][5][6] Tissue Mws constitute one of the most abundant populations of inflammatory cells in the uterus, and the numbers of these cells remain relatively constant in the decidua throughout gestation. 7,8 In normal pregnancies, the phenotype of uterine Mws is locally modified to acquire a type-2 phenotype, 9-11 which may contribute to trophoblast differentiation, support embryo implantation and supply growth factors to the placenta.…”

Section: Introductionmentioning

confidence: 99%

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The activating effect of IFN-γ on monocytes/macrophages is regulated by the LIF–trophoblast–IL-10 axis via Stat1 inhibition and Stat3 activation

et al. 2014

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Interferon gamma (IFN-c) and leukemia inhibitory factor (LIF) are key gestational factors that may differentially affect leukocyte function during gestation. Because IFN-c induces a pro-inflammatory phenotype in macrophages and because trophoblast cells are principal targets of LIF in the placenta, we investigated whether and how soluble factors from trophoblast cells regulate the effects of IFN-c on macrophage activation. IFN-c reduces macrophage motility, but enhances Stat1 activation, pro-inflammatory gene expression and cytotoxic functions. Soluble factors from villous cytotrophoblasts (vCT1LIF cells) and BeWo cells (BW/ST1LIF cells) that were differentiated in the presence of LIF inhibit macrophage Stat1 activation but inversely sustain Stat3 activation in response to IFN-c. vCT1LIF cells produce soluble factors that induce Stat3 activation; this effect is partially abrogated in the presence of neutralizing anti-interleukin 10 (IL-10) antibodies. Moreover, soluble factors from BW/ST1LIF cells reduce cell proliferation but enhance the migratory responses of monocytes. In addition, these factors reverse the inhibitory effect of IFN-c on monocyte/macrophage motility. BW/ST1LIF cells also generate IFN-c-activated macrophages with enhanced IL-10 expression, but reduced tumor-necrosis factor alpha (TNF-a), CD14 and CD40 expression as well as impaired cytotoxic function. Additional assays performed in the presence of neutralizing anti-IL-10 antibodies and exogenous IL-10 demonstrate that reduced macrophage cytotoxicity and proliferation, but increased cell motility result from the ability of trophoblast IL-10 to sustain Stat3 activation and suppress IFN-c-induced Stat1 activation. These in vitro studies are the first to describe the regulatory role of the LIF-trophoblast-IL-10 axis in the process of macrophage activation in response to pro-inflammatory cytokines.

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“…Some populations of macrophages are antimicrobial, some are wound healer and some populations are antiinflammatory or regulatory macrophage [2]. Macrophage-derived cytokines promote the phagocytic response through recruitment and production of fresh phagocytes and opsonizing molecules [3].…”

Section: Introductionmentioning

confidence: 99%

IL-3 and GM-CSF in combination alters protein tyrosine kinase activity of splenic macrophages in leukemic mice.

Singha¹,

Bhattacharjee²,

Maiti³

2015

Int Jour of Biomed Res

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Objectives: Murine macrophages were playing a key role against microbes and foreign particles as well as help in solid tumorigenesis in the host body. In this experiment we were trying to evaluate the protein tyrosine kinase (PTK) activity in macrophages from experimentally induced leukemic animal model. Methods: Balb/C mice were divided into four groups, two groups were challenged with N-N' ethyl nitrosourea (ENU) and two groups remained without ENU challenged condition. After confirmation of leukemia induction, one normal and one ENU challenged groups were received rmIL-3 and rmGM-CSF in combination for 4 consecutive days. Disease was confirmed by histological studies of peripheral blood and bone marrow smear. PTK activity assay were done using universal tyrosine kinase assay kit. Results: Protein tyrosine kinase (PTK) activity of macrophages was increased in leukemic animal significantly which were reduced after combination of IL-3 and GM-CSF treatment. IFN-γ level in blood serum was increased in leukemic mice and reinstates after treatment. Conclusion: Results suggest that, in leukemia reduced macrophage number can be increased by IL-3 and GM-CSF administration in combination but PTK activity is not involved to increase the number of macrophages. PTK activity may be involved in macrophage activation process in leukemic animal.

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Activation of Murine Macrophages

Cited by 29 publications

References 36 publications

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

The activating effect of IFN-γ on monocytes/macrophages is regulated by the LIF–trophoblast–IL-10 axis via Stat1 inhibition and Stat3 activation

IL-3 and GM-CSF in combination alters protein tyrosine kinase activity of splenic macrophages in leukemic mice.

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