title: 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.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu, 702-701, Republic of Korea.
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Lee
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Na
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D009113:Muramidase