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Keratinocytes treated with peptidoglycan from Staphylococcus aureus produce vascular endothelial growth factor, and its expression is amplified by the subsequent production of interleukin‐13
Author(s) -
RuízGonzález Verónica,
CancinoDiaz Juan C.,
RodríguezMartínez Sandra,
CancinoDiaz Mario E.
Publication year - 2009
Publication title -
international journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 93
eISSN - 1365-4632
pISSN - 0011-9059
DOI - 10.1111/j.1365-4632.2008.03924.x
Subject(s) - vascular endothelial growth factor , cathelicidin , hacat , tlr2 , medicine , microbiology and biotechnology , receptor , immunology , biology , innate immune system , cancer research , immune system , in vitro , vegf receptors , biochemistry
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.