title: Peptidoglycan from Staphylococcus aureus has an anti-apoptotic effect in HaCaT keratinocytes mediated by the production of the cellular inhibitor of apoptosis protein-2.
abstract: Colonization of epithelium by microorganisms leads to inflammatory responses. In some cases an anti-apoptotic response involving the cellular inhibitor of apoptosis protein-2 (cIAP-2) also occurs. Although strong expression of cIAP-2 has been observed in lesional skin from psoriatic patients and in HaCaT keratinocytes treated with peptidoglycan (PGN) from Staphylococcus aureus, anti-apoptotic responses induced in the skin by cIAP-2 have seldom been studied. In this study, the effect of PGN on TNF-α-induced apoptotic HaCaT keratinocytes was assessed. Morphological analysis, quantification of cells with DNA fragmentation and active caspase-3 detection was performed to assess apoptotic cell death. Greater LL-37 and cIAP-2 production was found in keratinocytes stimulated with PGN than in non-treated cells (P < 0.05). In comparison with cells treated with TNF-α only, a significant reduction in apoptotic cell death was observed when HaCaT were pretreated with PGN before inducing apoptosis with TNF-α (P < 0.05). In addition, an inhibitor of cIAP-2 activity (LCL161) stopped the PGN effect. These findings show that PGN from S. aureus has an anti-apoptotic effect in keratinocytes mediated by cIAP-2 production, suggesting that this anti-apoptotic activity could favor proliferation of keratinocytes in psoriasis.
authors.affiliation: Department of Immunology, National School of Biological Sciences-National Polytechnic Institute, Col. Santo Tomás, Del. Miguel Hidalgo, C.P., 11340.
authors.forename: Ernesto Antonio
authors.initials: EA
authors.lastname: Vázquez-Sánchez
authors.forename: Magdalena
authors.initials: M
authors.lastname: Rodríguez-Romero
authors.forename: Luvia Enid
authors.initials: LE
authors.lastname: Sánchez-Torres
authors.forename: Sandra
authors.initials: S
authors.lastname: Rodríguez-Martínez
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Cancino-Diaz
authors.forename: Octavio
authors.initials: O
authors.lastname: Rodríguez-Cortes
authors.forename: Eduardo Stalin
authors.initials: ES
authors.lastname: García-López
authors.forename: Mario Eugenio
authors.initials: ME
authors.lastname: Cancino-Diaz
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis* / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology*; D010457:Peptidoglycan / Q000378:metabolism* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D051034:Inhibitor of Apoptosis Proteins; D016209:Interleukin-8; D010457:Peptidoglycan; D014409:Tumor Necrosis Factor-alpha; D054804:Cathelicidins
keywords: apoptosis; cellular inhibitor of apoptosis protein-2; keratinocytes; peptidoglycan