Journal Article

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

Burke-Gaffney, Anne, Evans, Timothy W., Finney, Simon J., Leaver, Susannah K.

2012

Overview

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.

• Publisher: Springer-Verlag,Springer,Springer Nature B.V
• Subject: Acids / Activator protein 1 / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Anesthesiology / Animals / Biological and medical sciences / Biological response modifiers / Blood / Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis / Cell culture / chemokine KC / Chemokines / Chemokines - biosynthesis / Chemokines - drug effects / Chromatin remodeling / Critical Care Medicine / Cycloheximide / Cytokines / Cytokines - biosynthesis / Cytokines - drug effects / Emergency Medicine / Escherichia coli / Experimental / gamma -Interferon / Gene expression / Gram-positive bacteria / Intensive / Intensive care medicine / Interferon / Interleukin 10 / Interleukin 8 / Interleukins / Lipopolysaccharides / Lipopolysaccharides - pharmacology / Lipoteichoic acid / Macrophage inflammatory protein / Macrophages / Male / Medical sciences / Medicine / Medicine & Public Health / Mice / Mice, Inbred C57BL / Monocytes / mRNA stability / NF- Kappa B protein / Pain Medicine / Pediatrics / Peritoneum / Plasma levels / Pneumology/Respiratory System / Protein biosynthesis / Proteins / RNA / Sepsis / Staphylococcus aureus / Teichoic Acids - pharmacology / Transcription factors / Transfusions. Complications. Transfusion reactions. Cell and gene therapy / Tumor necrosis factor- alpha / Tumor necrosis factor-TNF