title: The antimicrobial peptide LL37 and its truncated derivatives potentiates proinflammatory cytokine induction by lipoteichoic acid in whole blood.
abstract: Interactions of bacterial and host products in activating the innate immune system is an important area to address. The role of lipoteichoic acid (LTA) in these interactions is particularly important because it is understudied in comparison to other factors. This study evaluated the effect of cationic peptides (CPs) on LTA-induced proinflammatory cytokine production in human whole blood and on purified leukocytes. Four different CPs of truncated derivatives from the known peptides LL37, BPI, and CP207 were used. Two of the CPs (IG33 and LL33), derivatives from LL37, potentiated S. aureus LTA induced TNFα, IL-6 and IL-1β production in whole blood. The release of TNFα was increased 30-fold after 16 hours incubation. Intact LL37 also increased LTA-induced TNFα and IL-1β in a time dependent manner. LTA in combination with either LL33 or IG23 demonstrated a synergistic enhanced TNFα and IL-1β secretion on isolated leukocytes but not on purified monocytes. When complexed with IG23 and LL33, the electrophoretic mobility of LTA was altered in a non-denaturating gel electrophoresis. LTA was disaggregated and migrated more rapidly, suggesting an amphiphilic effect of CPs on LTA. In conclusion, LTA synergizes with LL37 and its truncated derivatives and this may lead to proinflammatory cytokine production and cause problems in sepsis therapy.
authors.affiliation: Department of Biomedical Laboratory Science, Malmö University, Malmö, Sweden. Anna.Gustafsson@mah.se
authors.forename: Anna
authors.initials: A
authors.lastname: Gustafsson
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sigel
authors.forename: Lennart
authors.initials: L
authors.lastname: Ljunggren
mesh_terms: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006454:Hemoglobins / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D050505:Mutant Proteins / Q000494:pharmacology*; D013682:Teichoic Acids / Q000494:pharmacology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D016207:Cytokines; D006454:Hemoglobins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D050505:Mutant Proteins; D013682:Teichoic Acids; C009900:lipoteichoic acid