title: Inhibitory and anti-inflammatory effects of the Helicobacter pylori-derived antimicrobial peptide HPA3NT3 against Propionibacterium acnes in the skin.
abstract: BACKGROUND
  An effective treatment strategy for acne vulgaris is the reduction of Propionibacterium acnes in the skin. The Helicobacter pylori-derived synthetic antimicrobial peptide HPA3NT3 is a customized α-helical cationic peptide with antibacterial and anti-inflammatory activity.
  
  
  OBJECTIVE
  To examine the role of HPA3NT3 as a treatment against P. acnes-induced skin inflammation.
  
  
  METHODS
  Morphological alteration of individual P. acnes cells by HPA3NT3 was visualized by scanning electron microscopy. Modulation by HPA3NT3 of a number of P. acnes-induced innate immune responses was analysed in vitro using cultured normal human keratinocytes (HKs), and in vivo using the ICR mouse, a well-established model for P. acnes-induced skin inflammation.
  
  
  RESULTS
  The minimum inhibitory concentration of HPA3NT3 against P. acnes was low (0·4 μmol L(-1)). HPA3NT3 showed no cytotoxicity to HK cells at the concentrations used in our in vitro and in vivo studies. Treatment with HPA3NT3 in vitro induced morphological disruptions in P. acnes cells suggestive of a bactericidal effect. HPA3NT3 significantly decreased P. acnes-induced interleukin-8 expression and intracellular calcium mobilization in HK cells by inhibiting P. acnes-activated Toll-like receptor 2-mediated nuclear factor-κB signalling pathways. Intradermal injection of HPA3NT3 in vivo effectively decreased viable P. acnes, as well as erythema, swelling and inflammatory-cell infiltration in ICR mouse ears inoculated with P. acnes.
  
  
  CONCLUSIONS
  Our data suggest that HPA3NT3 has potential as a therapeutic agent for acne vulgaris due to its antimicrobial effects on P. acnes and its ability to block P. acnes-induced inflammation.
authors.affiliation: Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A; Department of Biochemistry, Chosun University School of Medicine, Gwangju, South Korea.
authors.forename: S
authors.initials: S
authors.lastname: Ryu
authors.forename: Y
authors.initials: Y
authors.lastname: Park
authors.forename: B
authors.initials: B
authors.lastname: Kim
authors.forename: S-M
authors.initials: SM
authors.lastname: Cho
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: H-H
authors.initials: HH
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Gurley
authors.forename: K
authors.initials: K
authors.lastname: Song
authors.forename: A
authors.initials: A
authors.lastname: Johnson
authors.forename: C A
authors.initials: CA
authors.lastname: Armstrong
authors.forename: P I
authors.initials: PI
authors.lastname: Song
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004890:Erythema / Q000188:drug therapy; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D007271:Injections, Intradermal; D016209:Interleukin-8 / Q000096:biosynthesis; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011425:Propionibacterium acnes / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012269:Ribosomal Proteins / Q000494:pharmacology*; D017192:Skin Diseases, Bacterial / Q000188:drug therapy*; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C530859:HPA3 peptide; D016209:Interleukin-8; D016328:NF-kappa B; D010446:Peptide Fragments; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D051195:Toll-Like Receptor 2; D002118:Calcium