Reduced substrate stiffness promotes M2-like macrophage activation and enhances peroxisome proliferator-activated receptor γ expression

Takayuki, Okamoto; Takagi, Yoshimi; Kawamoto, Eiji; Park, Eun Jeong; Usuda, Haruki; Wada, Koichiro; Shimaoka, Motomu

doi:10.1016/j.yexcr.2018.04.005

Cited by 78 publications

(66 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The conceptual perspective of this experiment, a so-called cell-centric perspective, assumes that a distinct cell phenotype demonstrates a particular response, and it presents the same response even when transferred into the tissue/matrix of different characteristics. On the other hand, monocytes were embedded, differentiated and activated within the testing materials [15,20,46], which is also shown in our study. This conceptual perspective, a so called tissue-centric perspective, assumes that the tissue shapes phenotypes and functions of cells to fulfill the tissue's need.…”

Section: General Discussion and Conclusionsupporting

confidence: 85%

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

Sapudom¹,

Mohamed

Garcia-Sabaté³

et al. 2020

Bioengineering

View full text Add to dashboard Cite

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.

show abstract

Section: General Discussion and Conclusionsupporting

confidence: 85%

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

Sapudom¹,

Mohamed

Garcia-Sabaté³

et al. 2020

Bioengineering

View full text Add to dashboard Cite

show abstract

“…The concept of tissue stiffness was proposed and that micro-environment and environmental signals were important and being observed as correlating with morbidity of chronic inflammation [83]. Changes in stiffness of micro-environment may be affected by the activation of fibroblasts, proteins, activation of extracellular matrix (ECM), and crosslinking of tissues.…”

Section: Role Of Macrophages In Obesity and Metabolic Diseasesmentioning

confidence: 99%

Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

Koh

Yang

Lai

et al. 2018

IJMS

View full text Add to dashboard Cite

Macrophages can polarize into two different states (M1 and M2), which play contrasting roles during pathogenesis or tissue damage. M1 polarized macrophages produce pro-inflammatory cytokines and mediators resulting in inflammation, while M2 macrophages have an anti-inflammatory effect. Secretion of appropriate cytokines and chemokines from macrophages can lead to the modification of the microenvironment for bridging innate and adaptive immune responses. Increasing evidence suggests that polarized macrophages are pivotal for disease progression, and the regulation of macrophage polarization may provide a new approach in therapeutic treatment of inflammation-related diseases, including cancer, obesity and metabolic diseases, fibrosis in organs, brain damage and neuron injuries, and colorectal disease. Polarized macrophages affect the microenvironment by secreting cytokines and chemokines while cytokines or mediators that are produced by resident cells or tissues may also influence macrophages behavior. The interplay of macrophages and other cells can affect disease progression, and therefore, understanding the activation of macrophages and the interaction between polarized macrophages and disease progression is imperative prior to taking therapeutic or preventive actions. Manipulation of macrophages can be an entry point for disease improvement, but the mechanism and potential must be understood. In this review, some advanced studies regarding the role of macrophages in different diseases, potential mechanisms involved, and intervention of drugs or phytochemicals, which are effective on macrophage polarization, will be discussed.

show abstract

“…This has been demonstrated by a substantial amount of studies investigating the effect of physical environmental factors on cellular functions 9,10 . It has previously been shown that the phenotype and the functionality of immune cells such as macrophages and dendritic cells are affected by stiffness [11][12][13] . It has also been reported that substrate elasticity has an impact on neutrophil adhesion, migration and chemotaxis [14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

Effect of Adhesion and Substrate Elasticity on Neutrophil Extracellular Trap Formation

Erpenbeck

Gruhn

Kudryasheva

et al. 2019

Preprint

View full text Add to dashboard Cite

Neutrophils are the most abundant type of white blood cells. As part of their immune defense mechanisms they are able to decondense and release their chromatin as neutrophil extracellular traps (NETs). This process (NETosis) also plays an important role in many chronic and inflammatory diseases such as atherosclerosis, rheumatoid arthritis, diabetes and cancer. For this reason, much effort has been invested into understanding biochemical signaling pathways in NETosis. However, the impact of the mechanical micro-environment and adhesion on NETosis is not well understood.Here, we study how adhesion and especially substrate elasticity affect NETosis. We employed polyacrylamide gels with varied elasticity (Young's modulus E) within the physiologically relevant range from 1 kPa to 128 kPa and coated the gels with integrin ligands (collagen I, fibrinogen).Neutrophils were cultured on these substrates and stimulated with chemical inducers of NETosis: phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS). Interestingly, PMA-induced NETosis was neither affected by substrate elasticity nor by different integrin ligands. In contrast, for LPS stimulation, NETosis rates increased with increasing substrate elasticity (E > 20 kPa). Additionally, we show that LPS-induced NETosis correlates with the cell contact area indicating that adhesion signaling and NETosis pathways are connected. On the other hand, PMA-induced NETosis did not require adhesion signaling.In summary, we show that LPS-induced NETosis depends on adhesion and substrate elasticity while PMA-induced NETosis is completely independent of adhesion.

show abstract

Reduced substrate stiffness promotes M2-like macrophage activation and enhances peroxisome proliferator-activated receptor γ expression

Cited by 78 publications

References 71 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

Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

Effect of Adhesion and Substrate Elasticity on Neutrophil Extracellular Trap Formation

Contact Info

Product

Resources

About