title: Doxycycline hyclate protects lipopolysaccharide-induced endothelial barrier dysfunction by inhibiting the activation of p38 mitogen-activated protein kinase.
abstract: Doxycycline hyclate (DOX-h) attenuates inflammatory conditions independent of its antimicrobial effect. This study aimed to observe the effects of DOX-h on lipopolysaccharide (LPS)-induced endothelial barrier dysfunction. The endothelial monolayer permeability of human umbilical vein endothelial cells (HUVECs) was monitored by transendothelial electrical resistance (TEER). The phosphorylation of mitogen-activated protein kinases (MAPKs) and the arrangement of F-actin were detected. The results showed that both pretreatment and simultaneous treatment with DOX-h markedly attenuated the LPS-induced reduction in TEER and the disorganization of F-actin on HUVECs in a dose- and time-dependent manner. LPS mediated the phosphorylation of all three MAPKs (p38, extracellular signal-regulated kinase (ERK)1/2, and c-Jun N-terminal kinase (JNK)), but DOX-h was only able to inhibit the LPS-induced phosphorylation of p38 and JNK. The data further suggested that DOX-h alleviated LPS-evoked TEER reduction and F-actin redistribution by inhibiting the phosphorylation of p38 and its downstream target, heat shock protein (HSP)27. Thus, DOX-h attenuates LPS-induced endothelial barrier dysfunction via inhibition of the p38 MAPK-HSP27-F-actin pathway.
authors.affiliation: First Clinical College of Medicine, Southern Medical University.
authors.forename: Jian-ling
authors.initials: JL
authors.lastname: Xia
authors.forename: Li-qun
authors.initials: LQ
authors.lastname: Wang
authors.forename: Li-li
authors.initials: LL
authors.lastname: Wu
authors.forename: Qiao-bing
authors.initials: QB
authors.lastname: Huang
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004318:Doxycycline / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D010539:Permeability / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D055551:HSP27 Heat-Shock Proteins; D008070:Lipopolysaccharides; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D004318:Doxycycline