TLR4, rather than TLR2, regulates wound healing through TGF-β and CCL5 expression

Hiraku Suga, Makoto Sugaya, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)


Background: Toll-like receptors (TLRs) have a crucial role in early host defense against invading pathogens. Recent studies suggest that TLRs play important roles in non-infections inflammation and tissue repair and regeneration. Objective: To determine the roles of TLR2 and TLR4 in mouse wound healing using TLR2-deficient (TLR2-/-), TLR4-deficient (TLR4-/-), and TLR2/TLR4-deficient (TLR2/4-/-) mice. Methods: Open wounds made in TLR2-/-, TLR4-/-, and TLR2/4-/- mice were examined clinically and histologically. Cytokine expression in the wounded skin was also investigated. TGF-β production from macrophages stimulated by hyaluronan, a ligand for TLR2 and TLR4, was evaluated by real-time PCR. Results: Wound areas in TLR2-/-, TLR4-/-, and TLR2/4-/- mice were larger than wild-type mice both at days 3 and 7 after wounding, accompanied by decreased numbers of infiltrating macrophages in the dermis and decreased TGF-β and CCL5 mRNA expression in the wounded skin. Immunohistochemistry showed decreased numbers of macrophages expressing TGF-β and reduced CCL5 expression by keratinocytes in the wounded skin from TLR2-/-, TLR4-/-, and TLR2/4-/- mice compared to wild-type mice. Moreover, TGF-β production from macrophages induced by hyaluronan stimulation in vitro was significantly decreased in the absence of TLRs, especially TLR4. Interestingly, macrophages and wounded skin from TLR2-/- mice showed decreased TLR4 mRNA expression compared to wild-type mice, suggesting that the effect of TLR2 deficiency was at least partially dependent on decrease in TLR4. Topical application of TGF-β and CCL5 significantly improved wound healing in TLR-deficient mice. Conclusion: TLR4, rather than TLR2, regulates wound healing through TGF-β and CCL5 expression.

Original languageEnglish
Pages (from-to)117-124
Number of pages8
JournalJournal of dermatological science
Issue number2
Publication statusPublished - 2014 Feb
Externally publishedYes


  • CCL5
  • TGF-β
  • TLR2
  • TLR4
  • Wound healing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology


Dive into the research topics of 'TLR4, rather than TLR2, regulates wound healing through TGF-β and CCL5 expression'. Together they form a unique fingerprint.

Cite this