Material stiffness influences the polarization state, function and migration mode of macrophages

Sridharan, Rukmani; Cavanagh, Brenton; Cameron, Andrew R.; Kelly, Daniel J.; O’Brien, Fergal J.

doi:10.1016/j.actbio.2019.02.048

Cited by 302 publications

(284 citation statements)

References 59 publications

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“…However, less is known on how tissue density modulates monocyte-to-macrophage activation and in turn their phenotypes and functions. Since tissue density is a surrogate for tissue stiffness, a number of studies aimed to study how mechanical properties of materials affect macrophage response [15]. However, these have often been investigated in 2D cell culture models, which may only partially reproduce the complexity of in vivo tissue [16,17].…”

Section: Introductionmentioning

confidence: 99%

Collagen Fibril Density Modulates Macrophage Activation and Cellular Functions during Tissue Repair

Sapudom¹,

Mohamed

Garcia-Sabaté³

et al. 2020

Bioengineering

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Monocytes circulate in the bloodstream, extravasate into the tissue and differentiate into specific macrophage phenotypes to fulfill the immunological needs of tissues. During the tissue repair process, tissue density transits from loose to dense tissue. However, little is known on how changes in tissue density affects macrophage activation and their cellular functions. In this work, monocytic cell line THP-1 cells were embedded in three-dimensional (3D) collagen matrices with different fibril density and were then differentiated into uncommitted macrophages (MPMA) using phorbol-12-myristate-13-acetate (PMA). MPMA macrophages were subsequently activated into pro-inflammatory macrophages (MLPS/IFNγ) and anti-inflammatory macrophages (MIL-4/IL-13) using lipopolysaccharide and interferon-gamma (IFNγ), and interleukin 4 (IL-4) and IL-13, respectively. Although analysis of cell surface markers, on both gene and protein levels, was inconclusive, cytokine secretion profiles, however, demonstrated differences in macrophage phenotype. In the presence of differentiation activators, MLPS/IFNγ secreted high amounts of IL-1β and tumor necrosis factor alpha (TNFα), while M0PMA secreted similar cytokines to MIL-4/IL-13, but low IL-8. After removing the activators and further culture for 3 days in fresh cell culture media, the secretion of IL-6 was found in high concentrations by MIL-4/IL-13, followed by MLPS/IFNγ and MPMA. Interestingly, the secretion of cytokines is enhanced with an increase of fibril density. Through the investigation of macrophage-associated functions during tissue repair, we demonstrated that M1LPS/IFNγ has the potential to enhance monocyte infiltration into tissue, while MIL-4/IL-13 supported fibroblast differentiation into myofibroblasts via transforming growth factor beta 1 (TGF-β1) in dependence of fibril density, suggesting a M2a-like phenotype. Overall, our results suggest that collagen fibril density can modulate macrophage response to favor tissue functions. Understanding of immune response in such complex 3D microenvironments will contribute to the novel therapeutic strategies for improving tissue repair, as well as guidance of the design of immune-modulated materials.

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Section: Introductionmentioning

confidence: 99%

Collagen Fibril Density Modulates Macrophage Activation and Cellular Functions during Tissue Repair

Sapudom¹,

Mohamed

Garcia-Sabaté³

et al. 2020

Bioengineering

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“…Macrophage produces nutrition factors and nerve toxicity factors, and shows the dual role of proinflammatory and anti-inflammatory, characterized by M1 and M2 polarization (32)(33)(34). M1 macrophage secretes high levels of oxide metabolites and proinflammatory factor, such as IL-6 and TNF-α.…”

Section: Discussionmentioning

confidence: 99%

Propofol inhibits inflammatory response by regulating the miR-494/ Nrdp1 pathway in ICH mice model

Shi

Xiong

Huang

et al. 2020

Preprint

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Background: Propofol is an anesthetic agent with neuro-protective effect in neuronal injury. However, the mechanism of propofol in M1 macrophage polarization following ICH has not been well studied. Ubiquitination mediated M1/M2 macrophage polarization plays important roles in pathogenesis of immune disease. The experiment analyzed anti-inflammatory effects of propofol in macrophages following ICH. Methods: In the experiment, macrophages were administrated with erythrocyte lysates, and then miR-494, Nrdp1 and M1 related markers were analyzed. In addition, brain inflammatory response, brain edema, and neurological functions of ICH mice were also assessed. Results: We found that propofol decreased miR-494 levels while increased Nrdp1 levels in macrophages after ICH. We also demonstrated that miR-494 inhibited Nrdp1 expression by directly binding its 3′-untranslated region. MiR-494 attenuated Nrdp1 levels and downstream proinflammatory factors production. Upregulation of Nrdp1 in macrophages significantly decreased M1 macrophage polarization. Conclusion: Taken together, these results suggest that propofol can attenuate the neuroinflammatory response of macrophages after ICH through regulation of the miR-494/Nrdp1 pathway.

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“…Macrophage produces nutrition factors and nerve toxicity factors, and shows the dual role of proin ammatory and anti-in ammatory, characterized by M1 and M2 polarization (33)(34)(35). M1 macrophage secretes high levels of oxide metabolites and proin ammatory factor, such as IL-6 and TNFα.…”

Section: Discussionmentioning

confidence: 99%

Propofol inhibits inflammatory response by regulating the miR-494/ Nrdp1 pathway in ICH mice model

Liu

Shi

et al. 2020

Preprint

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Background: Propofol is an anesthetic agent with neuro-protective effect in neuronal injury. However, the mechanism of propofol in M1 macrophage polarization following intracerebral hemorrhage (ICH) has not been well studied. Ubiquitination mediated M1/M2 macrophage polarization plays important roles in pathogenesis of immune disease. The experiment analyzed anti-inflammatory effects of propofol in macrophages following ICH. Methods: In the experiment, macrophages were administrated with erythrocyte lysates, and then miR-494, Neuregulin receptor degradation protein-1 (Nrdp1) and M1 related markers were analyzed. In addition, brain inflammatory response, brain edema, and neurological functions of ICH mice were also assessed. Results: We found that propofol decreased miR-494 levels while increased Nrdp1 levels in macrophages after ICH. We also demonstrated that miR-494 inhibited Nrdp1 expression by directly binding its 3′-untranslated region. MiR-494 attenuated Nrdp1 levels and downstream proinflammatory factors production. Upregulation of Nrdp1 in macrophages significantly decreased M1 macrophage polarization. Conclusion: Taken together, these results suggest that propofol can attenuate the neuroinflammatory response of macrophages after ICH through regulation of the miR-494/Nrdp1 pathway.

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Material stiffness influences the polarization state, function and migration mode of macrophages

Cited by 302 publications

References 59 publications

Collagen Fibril Density Modulates Macrophage Activation and Cellular Functions during Tissue Repair

Collagen Fibril Density Modulates Macrophage Activation and Cellular Functions during Tissue Repair

Propofol inhibits inflammatory response by regulating the miR-494/ Nrdp1 pathway in ICH mice model

Propofol inhibits inflammatory response by regulating the miR-494/ Nrdp1 pathway in ICH mice model

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