Next Article in Journal
Role of JAK/STAT3 Signaling in the Regulation of Metastasis, the Transition of Cancer Stem Cells, and Chemoresistance of Cancer by Epithelial–Mesenchymal Transition
Previous Article in Journal
ETV6/RUNX1 Fusion Gene Abrogation Decreases the Oncogenicity of Tumour Cells in a Preclinical Model of Acute Lymphoblastic Leukaemia
Open AccessFeature PaperArticle

Role of TLR4 Receptor Complex in the Regulation of the Innate Immune Response by Fibronectin

Department of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, NY 12208-3479, USA
Author to whom correspondence should be addressed.
Cells 2020, 9(1), 216; (registering DOI)
Received: 10 December 2019 / Revised: 7 January 2020 / Accepted: 10 January 2020 / Published: 15 January 2020
Chronic inflammation and subsequent tissue fibrosis are associated with a biochemical and mechanical remodeling of the fibronectin matrix. Due to its conformational lability, fibronectin is considerably stretched by the contractile forces of the fibrotic microenvironment, resulting in the unfolding of its Type III domains. In earlier studies, we have shown that a peptide mimetic of a partially unfolded fibronectin Type III domain, FnIII-1c, functions as a Damage Associated Molecular Pattern (DAMP) molecule to induce activation of a toll-like receptor 4 (TLR4)/NF-κB pathway and the subsequent release of fibro-inflammatory cytokines from human dermal fibroblasts. In the current study, we evaluated the requirement of the canonical TLR4/MD2/CD14 receptor complex in the regulation of FnIII-1c induced cytokine release. Using dermal fibroblasts and human embryonic kidney (HEK) cells, we found that all the components of the TLR4/MD2/CD14 complex were required for the release of the fibro-inflammatory cytokine, interleukin 8 (IL-8) in response to both FnIII-1c and the canonical TLR4 ligand, lipopolysaccharide (LPS). However, FnIII-1c mediated IL-8 release was strictly dependent on membrane-associated CD14, while LPS could use soluble CD14. These findings demonstrate that LPS and FnIII-1c share a similar but not identical mechanism of TLR4 activation in human dermal fibroblasts. View Full-Text
Keywords: fibronectin; TLR4; fibrosis; inflammation; IL-8; CD14 fibronectin; TLR4; fibrosis; inflammation; IL-8; CD14
Show Figures

Figure 1

MDPI and ACS Style

Zheng, M.; Ambesi, A.; J. McKeown-Longo, P. Role of TLR4 Receptor Complex in the Regulation of the Innate Immune Response by Fibronectin. Cells 2020, 9, 216.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Back to TopTop