Bowdish et al (2004) The human cationic peptide LL-37 induces activation of the extracellular signal regulated kinase and p38 kinase pathways in primary human monocytes. J. Immunol. 172;3758-3765

The human cationic peptide LL-37 induces activation of the extracellular signal regulated kinase and p38 kinase pathways in primary human monocytes.

Bowdish, D. M. E., Davidson, D. J., Speert, D. P. and Hancock, R. E. W.
J. Immunol. (2004) 172;3758-3765    PubMed
Davidson supported by funding from: Canadian CF Foundation

LL-37 is a cationic peptide that is found in the granules of neutrophils and is secreted by epithelial cells from a variety of tissues. Levels of LL-37 in vivo increase upon infection, and its production and secretion are increased upon stimulation with proinflammatory mediators. It has been postulated that LL-37 modulates the immune response by interacting with the effector cells of innate immunity; however, the mechanism of this interaction is unknown. LL-37 induced phosphorylation and activation of the mitogen-activated protein kinases, extracellular signal-regulated kinase 1/2 (ERK1/2) and p38, in human peripheral blood-derived monocytes and a human bronchial epithelial cell line, but not in B or T lymphocytes. Phosphorylation was not dependent on the G protein-coupled formyl peptide-like receptor 1, which was previously proposed to be the receptor for LL-37-induced chemotaxis on human monocytes and T cells. Activation of ERK1/2 and p38 was markedly increased by the presence of GM-CSF, but not M-CSF. Exposure to LL-37 also led to the activation of Elk-1, a transcription factor that is downstream of and activated by phosphorylated ERK1/2, the up-regulation of various Elk-1-controlled genes, and the transcription and secretion of IL-8. Inhibition of either p38 or ERK1/2 kinases led to a reduction in LL-37-induced IL-8 secretion and inhibition of the transcription of various chemokine genes. The ability of LL-37 to signal through these pathways has broad implications in immunity, monocyte activation, proliferation, and differentiation. PMID: 15004180
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