RRC ID 61026
Author Oda M, Domon H, Kurosawa M, Isono T, Maekawa T, Yamaguchi M, Kawabata S, Terao Y.
Title Streptococcus pyogenes Phospholipase A2 Induces the Expression of Adhesion Molecules on Human Umbilical Vein Endothelial Cells and Aorta of Mice.
Journal Front Cell Infect Microbiol
Abstract The Streptococcus pyogenes phospholipase A2 (SlaA) gene is highly conserved in the M3 serotype of group A S. pyogenes, which often involves hypervirulent clones. However, the role of SlaA in S. pyogenes pathogenesis is unclear. Herein, we report that SlaA induces the expression of intercellular adhesion molecule 1 (ICAM1) and vascular cell adhesion molecule 1 (VCAM1) via the arachidonic acid signaling cascade. Notably, recombinant SlaA induced ICAM1 and VCAM1 expression in human umbilical vein endothelial cells (HUVECs), resulting in enhanced adhesion of human monocytic leukemia (THP-1) cells. However, C134A, a variant enzyme with no enzymatic activity, did not induce such events. In addition, culture supernatants from S. pyogenes SSI-1 enhanced the adhesion of THP-1 cells to HUVECs, but culture supernatants from the ΔslaA isogenic mutant strain had limited effects. Aspirin, a cyclooxygenase 2 inhibitor, prevented the adhesion of THP-1 cells to HUVECs and did not induce ICAM1 and VCAM1 expression in HUVECs treated with SlaA. However, zileuton, a 5-lipoxygenase inhibitor, did not exhibit such effects. Furthermore, pre-administration of aspirin in mice intravenously injected with SlaA attenuated the transcriptional abundance of ICAM1 and VCAM1 in the aorta. These results suggested that SlaA from S. pyogenes stimulates the expression of adhesion molecules in vascular endothelial cells. Thus, SlaA contributes to the inflammation of vascular endothelial cells upon S. pyogenes infection.
Volume 7
Pages 300
Published 2017-1-1
DOI 10.3389/fcimb.2017.00300
PMID 28713783
PMC PMC5491884
MeSH Animals Aorta / drug effects* Arachidonic Acid / metabolism Aspirin / pharmacology Cell Adhesion Molecules / drug effects* Cell Adhesion Molecules / metabolism* DNA, Bacterial / genetics Endothelial Cells / drug effects* Gene Expression Human Umbilical Vein Endothelial Cells / drug effects* Human Umbilical Vein Endothelial Cells / pathology Humans Hydroxyurea / analogs & derivatives Hydroxyurea / pharmacology Inflammation / pathology Intercellular Adhesion Molecule-1 / drug effects Intercellular Adhesion Molecule-1 / metabolism Male Mice Mice, Inbred BALB C Monocytes Mutation Phospholipases A2 / genetics Phospholipases A2 / metabolism Phospholipases A2 / pharmacology* Recombinant Proteins Signal Transduction / drug effects Streptococcus pyogenes / enzymology* Streptococcus pyogenes / genetics THP-1 Cells / drug effects Vascular Cell Adhesion Molecule-1 / drug effects Vascular Cell Adhesion Molecule-1 / metabolism
IF 4.123
Human and Animal Cells THP-1(RCB1189)