Differences in lipopolysaccharide- and lipoteichoic acid-induced cytokine/chemokine expression

Intensive Care Med. 2012 Feb;38(2):324-32. doi: 10.1007/s00134-011-2444-5. Epub 2011 Dec 20.

Abstract

Purpose: To investigate differences in cytokine/chemokine release in response to lipoteichoic acid (LTA) or lipopolysaccharide (LPS) and contributing cellular mechanisms, in order to improve understanding of the pathogenesis of sepsis.

Methods: Levels of cytokines/chemokines were measured in plasma and peritoneal lavage fluid of 10-week-old male mice (C57/B16) following intraperitoneal injection of LTA or LPS (250 µg), and in supernatants of murine J774.2 cells, immortalised blood monocytes, or isolated human monocytes treated with LTA or LPS (0-10 µg/ml). The role of cytokine/chemokine messenger RNA (mRNA) stability versus nuclear factor-kappaB (NF-κB) and activator protein-1 (AP-1) in mediating cytokine/chemokine release in J774 cells was also assessed.

Results: In mice, plasma levels of keratinocyte-derived chemokine (KC), macrophage inflammatory protein (MIP)-2, interleukin (IL)-10, interferon (IFN)-γ and tumour necrosis factor-alpha (TNF-α) and peritoneal lavage fluid levels of KC, MIP-2 and TNF-α increased significantly 1 h after LPS. Only KC and MIP-2 levels increased 1 h after LTA. LPS-treated (10 μg/ml) J774 cells released MIP-2, IL-10, IFN-γ and TNF-α but not KC (24 h), whereas cells treated with 10 μg/ml LTA released only MIP-2. LPS-stimulated human monocytes released IL-10 and IL-8 (24 h); by contrast, LTA-treated cells released only IL-8. LPS and LTA activated NF-κB and AP-1 in J774 cells. The protein synthesis inhibitor cycloheximide abolished LPS-induced IL-10 mRNA expression and increased LTA- and LPS-induced mRNA for MIP-2 in J774 cells.

Conclusion: LTA and LPS, at clinically relevant concentrations, induced differential cytokine/chemokine release in vitro and in vivo, via effects distal to activation of NF-κB/AP-1 that might include chromatin remodelling or mRNA stability.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokines / biosynthesis*
  • Chemokines / drug effects*
  • Cytokines / biosynthesis*
  • Cytokines / drug effects*
  • Escherichia coli
  • Lipopolysaccharides / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Staphylococcus aureus
  • Teichoic Acids / pharmacology*

Substances

  • Chemokines
  • Cytokines
  • Lipopolysaccharides
  • Teichoic Acids
  • lipoteichoic acid