Keratinocytes treated with peptidoglycan from Staphylococcus aureus produce vascular endothelial growth factor, and its expression is amplified by the subsequent production of interleukin-13

Authors: Ruíz-González, Verónica; Cancino-Diaz, Juan C.; Rodríguez-Martínez, Sandra; Cancino-Diaz, Mario E.

Source: International Journal of Dermatology, Volume 48, Number 8, August 2009 , pp. 846-854(9)

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Abstract:

Background

Vascular endothelial growth factor (VEGF)-transgenic mice develop psoriasiform plaques that resemble human psoriasis, demonstrating that VEGF is an important factor in the development of psoriasis. In human keratinocytes, VEGF is regulated by human cathelicidin LL37, and the expression of this peptide, as well as interleukin-13 receptor-alpha1 (IL-13Rα1) and VEGF, is increased in psoriatic skin. Peptidoglycan (PGN) stimulates innate immunity, inducing cytokines and antimicrobial peptides (cathelicidins), but PGN can also activate psoriatic T-helper-1 (Th1) lymphocytes. As neither the bacterial component that induces LL37 and VEGF expression nor the function of IL-13 in keratinocytes has been clarified, the role of PGN in the induction of these molecules was evaluated in this work. Methods

HaCaT keratinocytes were treated with PGN from Staphylococcus aureus, recombinant VEGF (rVEGF), and recombinant IL-13 (rIL-13). The mRNA expression of LL37, VEGF, and IL-13 was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR), and VEGF and IL-13 production was measured by enzyme-linked immunosorbent assay (ELISA). Results

Keratinocytes treated with PGN show increased expression of LL37 at 24 h, VEGF at 36 h, and IL-13 at 72 h post-treatment. Anti-Toll-like receptor 2 (anti-TLR2) antibody blocked the production of these molecules. LL37 and VEGF expression in keratinocytes treated with PGN was dose dependent. rVEGF induced IL-13 production and rIL-13 induced VEGF production at 36 h. The anti-Flt-1 antibody blocked IL-13 expression. Conclusions

These results suggest that PGN from S. aureus can induce LL37 and VEGF expression in keratinocytes, and that this VEGF production can be amplified by subsequent IL-13 overproduction.

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-4632.2008.03924.x

Publication date: 2009-08-01

Keratinocytes treated with peptidoglycan from Staphylococcus aureus produce vascular endothelial growth factor, and its expression is amplified by the subsequent production of interleukin-13

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