PMID- 25899805 OWN - NLM STAT- MEDLINE DCOM- 20160624 LR - 20181113 IS - 1573-2576 (Electronic) IS - 0360-3997 (Linking) VI - 38 IP - 5 DP - 2015 Oct TI - Anti-Inflammatory Effects of Lysozyme Against HMGB1 in Human Endothelial Cells and in Mice. PG - 1911-24 LID - 10.1007/s10753-015-0171-8 [doi] AB - 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-kappaB (NF-kappaB), extracellular regulated kinases (ERK) 1/2 and production of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), 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. FAU - Lee, Wonhwa AU - Lee W AD - College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu, 702-701, Republic of Korea. FAU - Ku, Sae-Kwang AU - Ku SK FAU - Na, Dong Hee AU - Na DH FAU - Bae, Jong-Sup AU - Bae JS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - 0 (Anti-Inflammatory Agents) RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, human) RN - EC 3.2.1.17 (Muramidase) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Chickens MH - Dose-Response Relationship, Drug MH - Endothelium, Vascular/*drug effects/metabolism MH - HMGB1 Protein/*antagonists & inhibitors/*metabolism MH - Human Umbilical Vein Endothelial Cells/drug effects/metabolism MH - Humans MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Muramidase/*pharmacology EDAT- 2015/04/23 06:00 MHDA- 2016/06/25 06:00 CRDT- 2015/04/23 06:00 PHST- 2015/04/23 06:00 [entrez] PHST- 2015/04/23 06:00 [pubmed] PHST- 2016/06/25 06:00 [medline] AID - 10.1007/s10753-015-0171-8 [doi] PST - ppublish SO - Inflammation. 2015 Oct;38(5):1911-24. doi: 10.1007/s10753-015-0171-8.