CoChat
Sign Up
Cited by 168Wound Healing and TreatmentsNF-κB Signaling PathwaysTGF-β signaling in diseases

Absence of IL-1 Receptor Antagonist Impaired Wound Healing along with Aberrant NF-κB Activation and a Reciprocal Suppression of TGF-β Signal Pathway

Ishida, Yuko, Kondo, Toshikazu, Kimura, Akihiko, Matsushima, Kouji, Mukaida, Naofumi·2006·The Journal of Immunology
DOI 10.4049/jimmunol.176.9.5598
Open this paper in CoChat — free account

Abstract

Although enhanced expression of IL-1 family proteins, including IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1ra) during wound healing has been observed, the pathophysiological roles of these factors, particularly IL-1ra, still remain elusive. We explored skin wound-healing processes in IL-1ra-deficient mice. Compared to wild-type (WT) mice, IL-1ra-deficient mice exhibited impaired wound healing, as evidenced by attenuated collagen deposition and delayed neovascularization. In contrast, neutrophil recruitment was significantly exaggerated, with the augmented expression of IL-1s, TNF-α, and CXC chemokines, MIP-2 and KC, in IL-1ra-deficient mice compared with WT mice. Because the transcription of these proinflammatory cytokines and CXC chemokines requires the activation of NF-κB, a major target of IL-1- and TNF-α-mediated signal pathway, we examined the activation states of NF-κB. Nuclear translocation of NF-κB p65 was significantly enhanced and prolonged in IL-1ra-deficient mice, compared to that in WT mice. The cross-talk between NF-κB and TGF-β-mediated signals has been proposed based on in vitro observations. Indeed, compared to WT mice, the amounts of total and phosphorylated Smad2 and Smad3 were decreased with a reciprocal increase in the amount of Smad7 in skin wound sites of IL-1ra-deficient mice. Moreover, the gene expression of vascular endothelial growth factor, a target gene of TGF-β1, was decreased in IL-1ra-deficient mice. Thus, the absence of IL-1ra may suppress TGF-β-mediated signaling pathway, which is crucial for collagen deposition and vascular endothelial growth factor-mediated neovascularization in wound healing.

Integrity signals

Registry

Crossref · 10.4049/jimmunol.176.9.5598

Cites

63 of 63 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Mice deficient in the endogenous antagonist of IL-1R (IL-1ra) exhibit impaired wound healing compared with wild-type mice, as evidenced by attenuated collagen deposition and delayed neovascularization.

    “In contrast, mice deficient in the endogenous antagonist of IL-1R (IL-1ra) exhibit impaired wound healing compared with wild-type mice, as evidenced by attenuated collagen deposition and delayed neovascularization.56”

    From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [56]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Ishida, Y., Kondo, T., Kimura, A., Matsushima, K., & Mukaida, N.
Affiliations
  • Wakayama Medical University (JP)
  • The University of Tokyo (JP)
  • Kanazawa University (JP)
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2006-05-01
Volume
176
Issue
9
Pages
5598-5606
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.176.9.5598
OpenAlex
W1537718629
Cited by
168
References
62
Citations by year
2026: 2 · 2025: 1 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 11 · 2018: 6 · 2017: 16 · 2016: 6 · 2015: 9 · 2014: 10 · 2013: 11 · 2012: 11
FWCI
14.64
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
interleukin-1 receptor antagonist, wound healing, NF-κB activation, TGF-beta signaling, vascular endothelial growth factor, neovascularization, collagen deposition, neutrophil recruitment, CXC chemokines, TNF-α, IL-1 family cytokines, skin wound healing
MeSH terms
Animals, Collagen, Gene Expression Regulation, Interleukin-1, Leukocytes, Mice, Inbred BALB C, Sialoglycoproteins, Skin, Tumor Necrosis Factor-alpha, Wound Healing, Signal Transduction, Transforming Growth Factor beta, NF-kappa B, Mice, Knockout, Chemokines, CXC, Vascular Endothelial Growth Factor A, Mice, Smad Proteins, Interleukin 1 Receptor Antagonist Protein

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review