ArticleInternational immunology2018
Toll-like receptor signaling in macrophages is regulated by extracellular substrate stiffness and Rho-associated coiled-coil kinase (ROCK1/2).
Article in International immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 65 citations in OpenAlex.
- Review
- The role of extracellular matrix stiffness in regulating fibroblast behaviors and disease progression.Frontiers in immunology · 2026Review
- Mechanical interactions impact the functions of immune cells and their application in immunoengineering.Advanced therapeutics · 2025Article
- Perfluorocarbon-Loaded Poly(lactide-ACS applied polymer materials · 2025Article
- The Molecular Mechanism of Macrophages in Response to Mechanical Stress.Annals of biomedical engineering · 2025Review
- Advancements in adoptive CAR immune cell immunotherapy synergistically combined with multimodal approaches for tumor treatment.Bioactive materials · 2024Review
- Shear Stress Induces a Time-Dependent Inflammatory Response in Human Monocyte-Derived Macrophages.Annals of biomedical engineering · 2024Article
- The influence of biophysical niche on tumor-associated macrophages in liver cancer.Hepatology communications · 2024Review
- Exploiting Matrix Stiffness to Overcome Drug Resistance.ACS biomaterials science & engineering · 2024Review
- RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages.Journal of immunology research · 2024Article
- SUN1/2 controls macrophage polarization via modulating nuclear size and stiffness.Nature communications · 2023Article
- Macrophages and fibroblasts in foreign body reactions: How mechanical cues drive cell functions?Materials today. Bio · 2023Review
- A Case for Material Stiffness as a Design Parameter in Encapsulated Islet Transplantation.Tissue engineering. Part B, Reviews · 2023Review
- Mechanosensation to inflammation: Roles for YAP/TAZ in innate immune cells.Science signaling · 2023Review
- Modulation of Macrophage Function by Bioactive Wound Dressings with an Emphasis on Extracellular Matrix-Based Scaffolds and Nanofibrous Composites.Pharmaceutics · 2023Review
- Towards using 3D cellular cultures to model the activation and diverse functions of macrophages.Biochemical Society transactions · 2023Review
- Mechanical homeostasis imbalance in hepatic stellate cells activation and hepatic fibrosis.Frontiers in molecular biosciences · 2023Review
- The extracellular microenvironment in immune dysregulation and inflammation in retinal disorders.Frontiers in immunology · 2023Review
- Destructive fibrotic teamwork: how both microenvironment stiffness and profibrotic interleukin 13 impair alveolar macrophage phenotype and function.Biomaterials science · 2022Article
- Mechanoimmunology: Are inflammatory epigenetic states of macrophages tuned by biophysical factors?APL bioengineering · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Macrophages participate in immunity, tissue repair and tissue homeostasis. Activation of Toll-like receptors (TLRs) by conserved exogenous or endogenous structures initiates signaling cascades that result in the release of cytokines such as tumor necrosis factor α (TNFα). Extracellular substrate stiffness is known to regulate functions of non-immune cells through a process called mechanotransduction, yet less is known about how physical cues affect macrophage function or TLR signaling. To investigate this question, we cultured murine primary bone marrow-derived macrophages (BMMs) and RAW264.7 cells on fibronectin-coated polyacrylamide (PA) gels of defined stiffnesses (1, 20 and 150 kPa) that approximate the physical properties of physiologic tissues. BMMs on all gels were smaller and more circular than those on rigid glass. Macrophages on intermediate stiffness 20 kPa PA gels were slightly larger and less circular than those on either 1 or 150 kPa. Secretion of the pro-inflammatory cytokine, TNFα, in response to stimulation of TLR4 and TLR9 was increased in macrophages grown on soft gels versus more rigid gels, particularly for BMMs. Inhibition of the rho-associated coiled-coil kinase 1/2 (ROCK1/2), key mediators in cell contractility and mechanotransduction, enhanced release of TNFα in response to stimulation of TLR4. ROCK1/2 inhibition enhanced phosphorylation of the TLR downstream signaling molecules, p38, ERK1/2 and NFκB. Our data indicate that physical cues from the extracellular environment regulate macrophage morphology and TLR signaling. These findings have important implications in the regulation of macrophage function in diseased tissues and offer a novel pharmacological target for the manipulation of macrophage function in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.