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Cited by 176Cellular Mechanics and InteractionsImmune Response and InflammationNF-κB Signaling Pathways

Substrate Stiffness Regulates Proinflammatory Mediator Production through TLR4 Activity in Macrophages

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Previtera, Michelle L., Sengupta, Amitabha·2015·PLOS ONE
DOI 10.1371/journal.pone.0145813PMC PMC4692401
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Abstract

Clinical data show that disease adversely affects tissue elasticity or stiffness. While macrophage activity plays a critical role in driving disease pathology, there are limited data available on the effects of tissue stiffness on macrophage activity. In this study, the effects of substrate stiffness on inflammatory mediator production by macrophages were investigated. Bone marrow-derived macrophages were grown on polyacrylamide gels that mimicked the stiffness of a variety of soft biological tissues. Overall, macrophages grown on soft substrates produced less proinflammatory mediators than macrophages grown on stiff substrates when the endotoxin LPS was added to media. In addition, the pathways involved in stiffness-regulated proinflammation were investigated. The TLR4 signaling pathway was examined by evaluating TLR4, p-NF-κB p65, MyD88, and p-IκBα expression as well as p-NF-κB p65 translocation. Expression and translocation of the various signaling molecules were higher in macrophages grown on stiff substrates than on soft substrates. Furthermore, TLR4 knockout experiments showed that TLR4 activity enhanced proinflammation on stiff substrates. In conclusion, these results suggest that proinflammatory mediator production initiated by TLR4 is mechanically regulated in macrophages.

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Sorted by citations

Authors
Previtera, M. L., & Sengupta, A.
Affiliations
  • Seton Hall University (US)
  • John F. Kennedy Medical Center (US)
Corresponding author
Previtera, Michelle L.
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2015-12-28
Volume
10
Issue
12
Pages
e0145813
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0145813
PMC
PMC4692401
OpenAlex
W2197106873
Cited by
176
References
3
Citations by year
2026: 18 · 2025: 19 · 2024: 17 · 2023: 11 · 2022: 21 · 2021: 27 · 2020: 18 · 2019: 18 · 2018: 21 · 2017: 5 · 2016: 1
FWCI
4.80
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
substrate stiffness, macrophages, TLR4 signaling, p65 nuclear translocation, MyD88, IκBα phosphorylation, lipopolysaccharide, mechanotransduction, tissue stiffness, bone marrow-derived macrophages, polyacrylamide hydrogel
MeSH terms
NF-KappaB Inhibitor alpha, Animals, Cells, Cultured, Elasticity, Macrophages, Surface Properties, Tumor Necrosis Factor-alpha, Signal Transduction, Inflammation Mediators, I-kappa B Proteins, Toll-Like Receptor 4, Mice, Transcription Factor RelA, Myeloid Differentiation Factor 88, Biophysical Phenomena

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