The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses

Monisha G. Scott, Donald J. Davidson, Michael R. Gold, Dawn Bowdish, Robert Hancock

Research output: Contribution to journalArticle

468 Citations (Scopus)

Abstract

The role of LL-37, a human cationic antimicrobial peptide, in the immune system is not yet clearly understood. It is a widely expressed peptide that can be up-regulated during an immune response. In this report, we demonstrate that LL-37 is a potent antisepsis agent with the ability to inhibit macrophage stimulation by bacterial components such as LPS, lipoteichoic acid, and noncapped lipoarabinomannan. We also demonstrate that LL-37 protects mice against lethal endotoxemia. In addition to preventing macrophage activation by bacterial components, we hypothesized the LL-37 may also have direct effects on macrophage function. We therefore used gene expression profiling to identify macrophage functions that might be modulated by LL-37. These studies revealed that LL-37 directly up-regulates 29 genes and down-regulated another 20 genes. Among the genes predicted to be up-regulated by LL-37 were those encoding chemokines and chemokine receptors. Consistent with this, LL-37 up-regulated the expression of chemokines in macrophages and the mouse lung (monocyte chemoattractant protein 1), human A549 epithelial cells (IL-8), and whole human blood (monocyte chemoattractant protein 1 and IL-8), without stimulating the proinflammatory cytokine, TNFα. LL-37 also up-regulated the chemokine receptors CXCR-4, CCR2, and IL-8RB. These findings indicate that LL-37 may contribute to the immune response by limiting the damage caused by bacterial products and by recruiting immune cells to the site of infection so that they can clear the infection.

LanguageEnglish
Pages3883-3891
Number of pages9
JournalJournal of Immunology
Volume169
Issue number7
DOIs
Publication statusPublished - 1 Oct 2002
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Scott, Monisha G. ; Davidson, Donald J. ; Gold, Michael R. ; Bowdish, Dawn ; Hancock, Robert. / The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. In: Journal of Immunology. 2002 ; Vol. 169, No. 7. pp. 3883-3891.
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The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. / Scott, Monisha G.; Davidson, Donald J.; Gold, Michael R.; Bowdish, Dawn; Hancock, Robert.

In: Journal of Immunology, Vol. 169, No. 7, 01.10.2002, p. 3883-3891.

Research output: Contribution to journalArticle

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