title: The Toll-like receptor 1/2 agonists Pam(3) CSK(4) and human β-defensin-3 differentially induce interleukin-10 and nuclear factor-κB signalling patterns in human monocytes.
abstract: Human β-defensin 3 (hBD-3) activates antigen-presenting cells through Toll-like receptors (TLRs) 1/2. Several TLR1/2 agonists have been identified but little is known about how they might differentially affect cellular activation. We compared the effects of hBD-3 with those of another TLR1/2 agonist, Pam(3) CSK(4) , in human monocytes. Monocytes incubated with hBD-3 or Pam(3) CSK(4) produced interleukin-6 (IL-6), IL-8 and IL-1β, but only Pam(3) CSK(4) induced IL-10. The IL-10 induction by Pam(3) CSK(4) caused down-modulation of the co-stimulatory molecule, CD86, whereas CD86 expression was increased in monocytes exposed to hBD-3. Assessment of signalling pathways linked to IL-10 induction indicated that mitogen-activated protein kinases were activated similarly by hBD-3 or Pam(3) CSK(4) , whereas the non-canonical nuclear factor-κB pathway was only induced by Pam(3) CSK(4) . Our data suggest that the lack of non-canonical nuclear factor-κB signalling by hBD-3 could contribute to the failure of this TLR agonist to induce production of the anti-inflammatory cytokine, IL-10, in human monocytes.
authors: Division of Infectious Diseases, Department of Medicine, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH 44106, USA. ntf1@case.edu
authors: Nicholas T
authors: NT
authors: Funderburg
authors: Julie K
authors: JK
authors: Jadlowsky
authors: Michael M
authors: MM
authors: Lederman
authors: Zhimin
authors: Z
authors: Feng
authors: Aaron
authors: A
authors: Weinberg
authors: Scott F
authors: SF
authors: Sieg
mesh_terms: D051940:B7-2 Antigen / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D055666:Lipopeptides / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051194:Toll-Like Receptor 1 / Q000819:agonists* / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000276:immunology; D023083:beta-Defensins / Q000494:pharmacology*
chemical_list: D051940:B7-2 Antigen; C422950:DEFB103A protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D055666:Lipopeptides; D016328:NF-kappa B; C508075:Pam(3)CSK(4) peptide; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D023083:beta-Defensins; D016753:Interleukin-10; D020928:Mitogen-Activated Protein Kinases