Distinct strains of Propionibacterium acnes induce selective human beta-defensin-2 and interleukin-8 expression in human keratinocytes through toll-like receptors.
Acne is a chronic inflammatory disease of the pilosebaceous follicle. One of the main pathogenetic factors in acne is the increased proliferation of Propionibacterium acnes (P. acnes) in the pilosebaceous unit. We investigated whether direct interaction of P. acnes with keratinocytes might be involved in the inflammation and ductal hypercornification in acne. The capacities of different P. acnes strains to activate the innate immune response and the growth of cultured keratinocytes were investigated. We have found that two clinical isolates of P. acnes significantly induced human beta-defensin-2 (hBD2) messenger RNA (mRNA) expression; in contrast a third clinical isolate and the reference strain (ATCC11828) had no effect on hBD2 mRNA expression. In contrast, all four strains significantly induced the interleukin-8 (IL-8) mRNA expression. The P. acnes-induced increase in hBD2 and IL-8 gene expression could be inhibited by anti-Toll-like receptor 2 (TLR2) and anti-TLR4 neutralizing antibodies, suggesting that P. acnes-induced secretion of soluble factors in keratinocytes are both TLR2 and TLR4 dependent. In addition, the clinical isolate P. acnes (889) was capable of inducing keratinocyte cell growth in vitro. Our findings suggest that P. acnes modulates the antimicrobial peptide and chemokine expression of keratinocytes and thereby contributes to the recruitment of inflammatory cells to the sites of infections.
Nagy
István
I
Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary. nagyi@mail.derma.szote.u-szeged.hu
Pivarcsi
Andor
A
Koreck
Andrea
A
Széll
Márta
M
Urbán
Edit
E
Kemény
Lajos
L
D002470:Cell Survival; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000502:physiology*; D011425:Propionibacterium acnes / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity; D012333:RNA, Messenger / Q000032:analysis; D019105:Random Amplified Polymorphic DNA Technique; D011956:Receptors, Cell Surface / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D023083:beta-Defensins / Q000235:genetics* / Q000502:physiology
C106641:DEFB4A protein, human; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D023083:beta-Defensins