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Streptococcus pyogenes Phospholipase A 2 Induces the Expression of Adhesion Molecules on Human Umbilical Vein Endothelial Cells and Aorta of Mice.
- Source :
-
Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2017 Jun 30; Vol. 7, pp. 300. Date of Electronic Publication: 2017 Jun 30 (Print Publication: 2017). - Publication Year :
- 2017
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Abstract
- The Streptococcus pyogenes phospholipase A <subscript>2</subscript> (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 Δ slaA 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.
- Subjects :
- Animals
Arachidonic Acid metabolism
Aspirin pharmacology
DNA, Bacterial genetics
Gene Expression
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
Recombinant Proteins
Signal Transduction drug effects
Streptococcus pyogenes genetics
THP-1 Cells drug effects
Vascular Cell Adhesion Molecule-1 drug effects
Vascular Cell Adhesion Molecule-1 metabolism
Aorta drug effects
Cell Adhesion Molecules drug effects
Cell Adhesion Molecules metabolism
Endothelial Cells drug effects
Human Umbilical Vein Endothelial Cells drug effects
Phospholipases A2 pharmacology
Streptococcus pyogenes enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 2235-2988
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Frontiers in cellular and infection microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 28713783
- Full Text :
- https://doi.org/10.3389/fcimb.2017.00300