Collagen synthesis is suppressed in dermal fibroblasts by the human antimicrobial peptide LL-37

Hyun Jeong Park, Dae Ho Cho, Hee Jung Kim, Jun Young Lee, Baik Kee Cho, Sa Ik Bang, Sang Yong Song, Kenshi Yamasaki, Anna Di Nardo, Richard L. Gallo

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

LL-37 is a human cathelicidin antimicrobial peptide that is released in the skin after injury and acts to defend against infection and modulate the local cellular immune response. We observed in human dermal keloids that fibrosis was inversely related to the expression of cathelicidin and sought to determine how LL-37 influenced expression of types I and III collagen genes in dermal fibroblasts. At nano-molar concentrations, LL-37 inhibited baseline and transforming growth factor-β-induced collagen expression. At these concentrations, LL-37 also induced phosphorylation of extracellular signal-regulated kinase (ERK) within 30 minutes. Activation of ERK, and the activation of a G-protein-dependent pathway, was essential for inhibition of collagen expression as pertussis toxin or an inhibitor of ERK blocked the inhibitory effects of LL-37. c-Jun N-terminal kinase and p38 mitogen-activated protein kinase inhibitors did not alter the effects of cathelicidin. Silencing of the Ets-1 reversed inhibitory effects of LL-37. Taken together, these findings show that LL-37 can directly act on dermal fibroblasts and may have antifibrotic action during the wound repair process.

Original languageEnglish
Pages (from-to)843-850
Number of pages8
JournalJournal of Investigative Dermatology
Volume129
Issue number4
DOIs
Publication statusPublished - 2009 Jan 1
Externally publishedYes

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Extracellular Signal-Regulated MAP Kinases
Fibroblasts
Collagen
Skin
Chemical activation
Phosphorylation
Collagen Type III
JNK Mitogen-Activated Protein Kinases
Pertussis Toxin
Transforming Growth Factors
p38 Mitogen-Activated Protein Kinases
Protein Kinase Inhibitors
Collagen Type I
GTP-Binding Proteins
Keloid
Wounds and Injuries
Repair
Genes
Cellular Immunity
Fibrosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Collagen synthesis is suppressed in dermal fibroblasts by the human antimicrobial peptide LL-37. / Park, Hyun Jeong; Cho, Dae Ho; Kim, Hee Jung; Lee, Jun Young; Cho, Baik Kee; Bang, Sa Ik; Song, Sang Yong; Yamasaki, Kenshi; Di Nardo, Anna; Gallo, Richard L.

In: Journal of Investigative Dermatology, Vol. 129, No. 4, 01.01.2009, p. 843-850.

Research output: Contribution to journalArticle

Park, HJ, Cho, DH, Kim, HJ, Lee, JY, Cho, BK, Bang, SI, Song, SY, Yamasaki, K, Di Nardo, A & Gallo, RL 2009, 'Collagen synthesis is suppressed in dermal fibroblasts by the human antimicrobial peptide LL-37', Journal of Investigative Dermatology, vol. 129, no. 4, pp. 843-850. https://doi.org/10.1038/jid.2008.320
Park, Hyun Jeong ; Cho, Dae Ho ; Kim, Hee Jung ; Lee, Jun Young ; Cho, Baik Kee ; Bang, Sa Ik ; Song, Sang Yong ; Yamasaki, Kenshi ; Di Nardo, Anna ; Gallo, Richard L. / Collagen synthesis is suppressed in dermal fibroblasts by the human antimicrobial peptide LL-37. In: Journal of Investigative Dermatology. 2009 ; Vol. 129, No. 4. pp. 843-850.
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