Anti-Inflammatory Effects of Lysozyme Against HMGB1 in Human Endothelial Cells and in Mice.

Abstract

High mobility group box 1 (HMGB1) was recently shown to be an important extracellular mediator of severe vascular inflammatory disease, sepsis. Lysozyme protects us from the ever-present danger of bacterial infection and binds to bacterial lipopolysaccharide (LPS) with a high affinity. Here, we show, for the first time, the anti-septic effects of lysozyme in HMGB1-mediated inflammatory responses in vitro and in vivo. The data showed that lysozyme posttreatment suppressed LPS-mediated release of HMGB1 and HMGB1-mediated cytoskeletal rearrangement. Lysozyme also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in human endothelial cells. In addition, lysozyme inhibited the HMGB1-mediated activation of Akt, nuclear factor-κB (NF-κB), extracellular regulated kinases (ERK) 1/2 and production of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and chemoattractant protein-1 (MCP-1) in HUVECs. Furthermore, lysozyme reduced the cecal ligation and puncture (CLP)-induced release of HMGB1, migration of leukocytes, septic mortality, and pulmonary damage in mice. Collectively, these results suggest lysozyme as a candidate therapeutic agent for the treatment of vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.

• Authors: Wonhwa Lee, Sae-Kwang Ku, Dong Hee Na, Jong-Sup Bae
• Journal: Inflammation (Inflammation) Vol. 38 Issue 5 Pg. 1911-24 (Oct 2015) ISSN: 1573-2576 [Electronic] United States
• PMID: 25899805 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• HMGB1 Protein
• HMGB1 protein, human
• Muramidase

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Chickens
• Dose-Response Relationship, Drug
• Endothelium, Vascular (drug effects, metabolism)
• HMGB1 Protein (antagonists & inhibitors, metabolism)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Muramidase (pharmacology)