title: Keratinocytes treated with peptidoglycan from Staphylococcus aureus produce vascular endothelial growth factor, and its expression is amplified by the subsequent production of interleukin-13.
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-13Ralpha1) 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.
authors: Immunology Department, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico.
authors: Verónica
authors: V
authors: Ruíz-González
authors: Juan C
authors: JC
authors: Cancino-Diaz
authors: Sandra
authors: S
authors: Rodríguez-Martínez
authors: Mario E
authors: ME
authors: Cancino-Diaz
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D001424:Bacterial Infections / Q000150:complications / Q000276:immunology; D054804:Cathelicidins; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010457:Peptidoglycan / Q000494:pharmacology*; D011565:Psoriasis / Q000150:complications / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D018793:Interleukin-13; D010457:Peptidoglycan; D012333:RNA, Messenger; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A