Microvesicles carrying LRP5 induce macrophage polarization to an anti‐inflammatory phenotype

Macrophages are phagocytic cells involved in maintaining tissue homeostasis and defense against pathogens. Macrophages may be polarized into different functionally specialized subsets. M2c macrophages arise following stimulation with IL-10 or TGF-β and mediate anti-inflammatory and tissue repair functions. M2c macrophages remain poorly characterized in the pig, thus we investigated the impact of these regulatory cytokines on porcine monocyte-derived macrophages (moMΦ). The phenotype and functionality of these cells was characterized though confocal microscopy, flow cytometry, ELISA, and RT-qPCR. Both cytokines induced CD14 and MHC II DR down-regulation and reduced IL-6, TNF-α, and CD14 expression, suggestive of an anti-inflammatory phenotype. Interestingly, neither IL-10 or TGF-β were able to trigger IL-10 induction or release by moMΦ. Differences between these cytokines were observed: stimulation with IL-10, but not TGF-β, induced up-regulation of both CD16 and CD163 on moMΦ. In addition, IL-10 down-regulated expression of IL-1β and IL-12p40 4h post-stimulation and induced a stronger impairment of moMΦ ability to respond to either TLR2 or TLR4 agonists. Overall, our results provide an overview of porcine macrophage polarization by two immunosuppressive cytokines, revealing differences between IL-10 and TGF-β, and reporting some peculiarity of swine, which should be considered in translational studies.

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Wnt/β-catenin signaling regulates lipopolysaccharide-altered polarizations of RAW264.7 cells and alveolar macrophages in mouse lungs

European Journal of Inflammation ◽

10.1177/20587392211059362 ◽

2021 ◽

Vol 19 ◽

pp. 205873922110593

Author(s):

Jiali Yang ◽

Ying Wang ◽

Dandan Yang ◽

Jia Ma ◽

Shuang Wu ◽

...

Keyword(s):

Alveolar Macrophage ◽

Alveolar Macrophages ◽

Macrophage Polarization ◽

Raw264.7 Cells ◽

M1 Polarization ◽

Inflammatory Phenotype ◽

Inflammatory State ◽

Anti Inflammatory

Introduction Macrophages are capable of exerting both proinflammatory and anti-inflammatory functions in response to distinct environmental stimuli, by polarizing into classically inflammatory state (M1) and anti-inflammatory phenotype (M2), respectively. The Wnt/β-catenin signaling plays an important role in the tissue homeostasis and immune regulations, including the macrophage polarizations. However, the molecular mechanism of Wnt/β-catenin signaling in regulating alveolar macrophage polarization in an inflammatory state remains unclear. Methods The Wnt/β-catenin signaling-altered phenotypes of murine macrophage-like RAW264.7 cells in vitro and alveolar macrophage in vivo in both of naïve and lipopolysaccharide-induced inflammation states were accessed by immunoblotting and immunostaining assays. Results The activation of Wnt/β-catenin signaling inhibited macrophage M1 polarization, but promoted alternative M2 polarization in murine RAW264.7 cells under a naïve state. Interestingly, in an LPS-induced inflammation condition, the enhanced Wnt/β-catenin activity suppressed both M1 and M2 polarizations in RAW264.7 cells in vitro, and primary alveolar macrophages of LPS-challenged mice in vivo. Molecular analysis further demonstrated an involvement of Stat signing in regulating Wnt/β-catenin signaling-altered polarizations in mouse alveolar macrophages. Conclusion These results suggest a mechanism by which Wnt/β-catenin signaling modulates macrophage polarization in an inflammation state by regulating the Stat signaling pathway.

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Cold Atmospheric Pressure Plasma Treatment Modulates Human Monocytes/Macrophages Responsiveness

Plasma ◽

10.3390/plasma1020023 ◽

2018 ◽

Vol 1 (2) ◽

pp. 261-276 ◽

Cited By ~ 6

Author(s):

Letizia Crestale ◽

Romolo Laurita ◽

Anna Liguori ◽

Augusto Stancampiano ◽

Maria Talmon ◽

...

Keyword(s):

Plasma Treatment ◽

Macrophage Polarization ◽

Immune Surveillance ◽

Atmospheric Pressure Plasma ◽

Atmospheric Plasma ◽

Viability Analysis ◽

Inflammatory Phenotype ◽

Cold Atmospheric Pressure Plasma ◽

Anti Inflammatory ◽

Inflammatory Macrophages

Monocytes are involved in innate immune surveillance, establishment and resolution on inflammation, and can polarize versus M1 (pro-inflammatory) or M2 (anti-inflammatory) macrophages. The possibility to control and drive immune cells activity through plasma stimulation is therefore attractive. We focused on the effects induced by cold-atmospheric plasma on human primary monocytes and monocyte-derived macrophages. Monocytes resulted more susceptible than monocyte-derived macrophages to the plasma treatment as demonstrated by the increase in reactive oxygen (ROS) production and reduction of viability. Macrophages instead were not induced to produce ROS and presented a stable viability. Analysis of macrophage markers demonstrated a time-dependent decrease of the M1 population and a correspondent increase of M2 monocyte-derived macrophages (MDM). These findings suggest that plasma treatment may drive macrophage polarization towards an anti-inflammatory phenotype.

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Supramolecular copolymer modified statins-loaded discoidal rHDLs for atherosclerotic anti-inflammatory therapy by cholesterol efflux and M2 macrophage polarization

Biomaterials Science ◽

10.1039/d1bm00610j ◽

2021 ◽

Author(s):

Qiqi Zhang ◽

Jianhua He ◽

Fengfei Xu ◽

Xinya Huang ◽

Yanyan Wang ◽

...

Keyword(s):

Essential Role ◽

Macrophage Polarization ◽

M2 Macrophage ◽

Macrophage Phenotype ◽

Cholesterol Removal ◽

Atherosclerosis Progression ◽

Inflammatory Phenotype ◽

M2 Macrophage Polarization ◽

Anti Inflammatory ◽

Inflammatory Macrophage

Foam cells with the pro-inflammatory macrophage phenotype (M1) play an essential role in atherosclerosis progression. Either cellular cholesterol removal or drug intervention was reported to polarize M1 into anti-inflammatory phenotype...

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Inhibition of SIK2 and SIK3 during differentiation enhances the anti-inflammatory phenotype of macrophages

Biochemical Journal ◽

10.1042/bcj20160646 ◽

2017 ◽

Vol 474 (4) ◽

pp. 521-537 ◽

Cited By ~ 18

Author(s):

Nicola J. Darling ◽

Rachel Toth ◽

J. Simon C. Arthur ◽

Kristopher Clark

Keyword(s):

Inflammatory Cytokines ◽

Drug Targets ◽

Macrophage Polarization ◽

Macrophage Phenotype ◽

Integral Role ◽

Inflammatory Phenotype ◽

Low Levels ◽

Anti Inflammatory ◽

Factor Α ◽

Pro Inflammatory Cytokines

The salt-inducible kinases (SIKs) control a novel molecular switch regulating macrophage polarization. Pharmacological inhibition of the SIKs induces a macrophage phenotype characterized by the secretion of high levels of anti-inflammatory cytokines, including interleukin (IL)-10, and the secretion of very low levels of pro-inflammatory cytokines, such as tumour necrosis factor α. The SIKs, therefore, represent attractive new drug targets for the treatment of macrophage-driven diseases, but which of the three isoforms, SIK1, SIK2 or SIK3, would be appropriate to target remains unknown. To address this question, we developed knock-in (KI) mice for SIK1, SIK2 and SIK3, in which we introduced a mutation that renders the enzymes catalytically inactive. Characterization of primary macrophages from the single and double KI mice established that all three SIK isoforms, and in particular SIK2 and SIK3, contribute to macrophage polarization. Moreover, we discovered that inhibition of SIK2 and SIK3 during macrophage differentiation greatly enhanced the production of IL-10 compared with their inhibition in mature macrophages. Interestingly, macrophages differentiated in the presence of SIK inhibitors, MRT199665 and HG-9-91-01, still produced very large amounts of IL-10, but very low levels of pro-inflammatory cytokines, even after the SIKs had been reactivated by removal of the drugs. Our data highlight an integral role for SIK2 and SIK3 in innate immunity by preventing the differentiation of macrophages into a potent and stable anti-inflammatory phenotype.

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Macrophage polarization is linked to Ca2+-independent phospholipase A2β-derived lipids and cross-cell signaling in mice

The Journal of Lipid Research ◽

10.1194/jlr.ra119000281 ◽

2019 ◽

Vol 61 (2) ◽

pp. 143-158 ◽

Cited By ~ 3

Author(s):

Alexander J. Nelson ◽

Daniel J. Stephenson ◽

Christopher L. Cardona ◽

Xiaoyong Lei ◽

Abdulaziz Almutairi ◽

...

Keyword(s):

Inflammatory Responses ◽

Macrophage Polarization ◽

Lipid Mediator ◽

Inflammatory Phenotype ◽

M1 Phenotype ◽

Anti Inflammatory ◽

First Time ◽

Genotypic Control ◽

Hydrolysis Of ◽

Phospholipases A

Phospholipases A2 (PLA2s) catalyze hydrolysis of the sn-2 substituent from glycerophospholipids to yield a free fatty acid (i.e., arachidonic acid), which can be metabolized to pro- or anti-inflammatory eicosanoids. Macrophages modulate inflammatory responses and are affected by Ca2+-independent phospholipase A2 (PLA2)β (iPLA2β). Here, we assessed the link between iPLA2β-derived lipids (iDLs) and macrophage polarization. Macrophages from WT and KO (iPLA2β−/−) mice were classically M1 pro-inflammatory phenotype activated or alternatively M2 anti-inflammatory phenotype activated, and eicosanoid production was determined by ultra-performance LC ESI-MS/MS. As a genotypic control, we performed similar analyses on macrophages from RIP.iPLA2β.Tg mice with selective iPLA2β overexpression in β-cells. Compared with WT, generation of select pro-inflammatory prostaglandins (PGs) was lower in iPLA2β−/−, and that of a specialized pro-resolving lipid mediator (SPM), resolvin D2, was higher; both changes are consistent with the M2 phenotype. Conversely, macrophages from RIP.iPLA2β.Tg mice exhibited an opposite landscape, one associated with the M1 phenotype: namely, increased production of pro-inflammatory eicosanoids (6-keto PGF1α, PGE2, leukotriene B4) and decreased ability to generate resolvin D2. These changes were not linked with secretory PLA2 or cytosolic PLA2α or with leakage of the transgene. Thus, we report previously unidentified links between select iPLA2β-derived eicosanoids, an SPM, and macrophage polarization. Importantly, our findings reveal for the first time that β-cell iPLA2β-derived signaling can predispose macrophage responses. These findings suggest that iDLs play critical roles in macrophage polarization, and we posit that they could be targeted therapeutically to counter inflammation-based disorders.

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Lentivirus delivery of IL-10 to promote and sustain macrophage polarization towards an anti-inflammatory phenotype

Biotechnology and Bioengineering ◽

10.1002/bit.25175 ◽

2014 ◽

Vol 111 (6) ◽

pp. 1210-1221 ◽

Cited By ~ 62

Author(s):

R.M. Boehler ◽

R. Kuo ◽

S. Shin ◽

A.G. Goodman ◽

M.A. Pilecki ◽

...

Keyword(s):

Macrophage Polarization ◽

Inflammatory Phenotype ◽

Anti Inflammatory

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Curcumin Modulates the Crosstalk Between Macrophages and Bone Mesenchymal Stem Cells to Ameliorate Osteogenesis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.634650 ◽

2021 ◽

Vol 9 ◽

Author(s):

Songfeng Chen ◽

Hang Liang ◽

Yanhui Ji ◽

Hongwei Kou ◽

Chi Zhang ◽

...

Keyword(s):

Inflammatory Response ◽

Osteogenic Differentiation ◽

Macrophage Polarization ◽

Bone Mesenchymal Stem Cells ◽

Tnf Α ◽

Inflammatory Phenotype ◽

Phenotype Switch ◽

Anti Inflammatory ◽

Inflammatory Macrophage ◽

Inflammatory Effect

Bone healing is thought to be influenced by the cross-talk between bone forming and immune cells. In particular, macrophages play a crucial role in the regulation of osteogenesis. Curcumin, the major bioactive polyphenolic ingredient of turmeric, has been shown to regulate inflammatory response and osteogenic activities. However, whether curcumin could regulate macrophage polarization and subsequently influence osteogenesis remain to be elucidated. In this study, the potential immunomodulatory capability of curcumin on inflammatory response and phenotype switch of macrophages and the subsequent impact on osteogenic differentiation of MSCs are investigated. We demonstrated that curcumin exhibited significant anti-inflammatory effect by polarizing the macrophages toward anti-inflammatory phenotype, with increased expression of IL-4, IL-10, and CD206, and decreased expression of IL-1β, TNF-α, CCR7, and iNOS. In addition, curcumin could improve the osteo-immune microenvironment via promoting osteogenesis-related regenerative cytokine BMP-2 and TGF-β production. Moreover, the co-cultured test of macrophages and BMSCs showed that curcumin-modulated macrophages conditioned medium could promote osteogenic differentiation of BMSCs with increased gene (ALP, Runx-2, OCN, and OPN) and protein (Runx-2 and OCN) expression levels, enhanced ALP activity, and obvious formation of mineralized nodules. Taken together, with the interaction between curcumin-conditioned macrophage and curcumin-stimulated BMSCs, curcumin could remarkably enhance the osteogenic differentiation of BMSCs in LPS-activated inflammatory macrophage-BMSCs coculture system.

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