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Antimicrobial peptide LL 37 promotes vascular endothelial growth factor‐ A expression in human periodontal ligament cells
Author(s) -
Kittaka M.,
Shiba H.,
Kajiya M.,
Ouhara K.,
Takeda K.,
Kanbara K.,
Fujita T.,
Kawaguchi H.,
Komatsuzawa H.,
Kurihara H.
Publication year - 2013
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2012.01524.x
Subject(s) - angiogenesis , vascular endothelial growth factor , mapk/erk pathway , cytokine , periodontal fiber , microbiology and biotechnology , vascular endothelial growth factor a , biology , chemistry , signal transduction , cancer research , immunology , medicine , vegf receptors , dentistry
Background and Objective LL 37, originally found in the innate immune system, is a robust antimicrobial peptide. LL 37 exhibits multiple bio‐functions in various cell types, such as migration, cytokine production, apoptosis, and angiogenesis besides its antimicrobial activity Periodontal ligament ( PL ) cells play a pivotal role in periodontal tissue regeneration. Based on these findings, we hypothesized that LL 37 can regulate PL cell function to promote regeneration of periodontal tissue. To prove this hypothesis, we investigated the effect of LL 37 on the potent angiogenic inducer vascular endothelial growth factor ( VEGF ) expression in cultures of human PL ( HPL ) cells because neovascularization is indispensable for the progress of tissue regeneration. Moreover, we investigated the signaling cascade associated with LL 37‐induced VEGF expression. Material and Method HPL cells were treated with synthesized LL 37 in the presence or absence of PD 98059, a MEK ‐ ERK inhibitor, or PDTC , an NF ‐κB inhibitor. VEGF expression levels were assessed by real‐time polymerase chain reaction analysis and an enzyme‐linked immunoassay. Phosphorylation levels of ERK 1/2 or NF ‐κB p65 were determined by Western blotting. Results LL 37 upregulated VEGF ‐ A expression at the mRNA and protein levels in HPL cells, while VEGF ‐ B mRNA expression was not affected. Both ERK and NF‐κB inhibitors clearly abrogated the increase in VEGF ‐ A levels induced by LL 37 in HPL cells. Importantly, LL 37 increased phosphorylated levels of ERK 1/2 and NF ‐κ B p65 in HPL cells. Conclusion LL 37 induces VEGF ‐A production in HPL cells via ERK and NF ‐κB signaling cascades, which may result in angiogenesis, thereby contributing to periodontal regeneration.