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Integrated proteomic analysis of tumor necrosis factor α and interleukin 1β-induced endothelial inflammation
- Source :
- Journal of Proteomics, 92, 89. Elsevier, Journal of proteomics, 192, 89-101. Elsevier
- Publication Year :
- 2018
-
Abstract
- The vascular endothelium provides a unique interaction plane for plasma proteins and leukocytes in inflammation. The pro-inflammatory cytokines Tumor Necrosis Factor α (TNFα) and interleukin 1β (IL-1β) have a profound effect on endothelial cells, which includes increased levels of adhesion molecules and a disrupted barrier function. To assess the endothelial response to these cytokines at the protein level, we evaluated changes in the whole proteome, cell surface proteome and phosphoproteome after 24 h of cytokine treatment. The effects of TNFα and IL-1β on endothelial cells were strikingly similar and included changes in proteins not previously associated with endothelial inflammation. Temporal profiling revealed time-dependent proteomic changes, including a limited number of early responsive proteins such as adhesion receptors ICAM1 and SELE. In addition, this approach uncovered a greater number of late responsive proteins, including proteins related to self-antigen peptide presentation, and a transient increase in ferritin. Peptide-based cell surface proteomics revealed extensive changes at the cell surface, which were in agreement with the whole proteome. In addition, site-specific changes within ITGA5 and ICAM1 were detected. Combined, our integrated proteomic data provide detailed information on endothelial inflammation, emphasize the role of the extracellular matrix therein, and include potential targets for therapeutic intervention. SIGNIFICANCE: Pro-inflammatory cytokines induce the expression of cell adhesion molecules in vascular endothelial cells. These molecules mediate the adhesion and migration of immune cells across the vessel wall, which is a key process to resolve infections in the underlying tissue. Dysregulation of endothelial inflammation can contribute to vascular diseases and the vascular endothelium is therefore an attractive target to control inflammation. Current strategies targeting endothelial adhesion molecules, including PECAM, CD99, ICAM1 and VCAM1 do not completely prevent transmigration. To identify additional therapeutic targets, we mapped the endothelial proteome after pro-inflammatory cytokine treatment. In addition to the whole proteome, we assessed the surface proteome to focus on cell adhesion molecules, and the phosphoproteome to uncover protein activation states. Here, we present an integrated overview of affected processes which further improves our understanding of endothelial inflammation and may eventually aid in therapeutic intervention of imbalanced inflammation.
- Subjects :
- 0301 basic medicine
Proteomics
Endothelium
Phosphoproteomics
medicine.medical_treatment
Cell surface proteomics
Interleukin-1beta
Biophysics
Inflammation
Biochemistry
Extracellular matrix
03 medical and health sciences
medicine
TNFα
Humans
Cells, Cultured
030102 biochemistry & molecular biology
Chemistry
Cell adhesion molecule
Tumor Necrosis Factor-alpha
Endothelial Cells
Cell biology
030104 developmental biology
Cytokine
medicine.anatomical_structure
IL-1β
Proteome
Tumor necrosis factor alpha
medicine.symptom
Cell Adhesion Molecules
Subjects
Details
- ISSN :
- 18767737 and 18743919
- Volume :
- 192
- Database :
- OpenAIRE
- Journal :
- Journal of proteomics
- Accession number :
- edsair.doi.dedup.....72e00e7151709cd4aad4de4a4e909704