Related Experiment Video
Updated: Apr 28, 2026
On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
TNF-α-induced ICAM-1 expression and monocyte adhesion in human RPE cells is mediated in part through autocrine VEGF
Peeradech Thichanpiang1, Steven J Harper2, Kanokpan Wongprasert3
1Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand ; Microvascular Research Laboratories, Department of Physiology and Pharmacology, School of Veterinary Sciences, University of Bristol, Bristol, UK.
Purpose:
Local inflammation at the RPE cell layer is associated with inflammatory cell migration and secretion of proinflammatory cytokines such as tumor necrosis factor (TNF)-α. TNF-α upregulates intercellular adhesion molecule (ICAM)-1 expression on the RPE, which allows lymphocyte function-associated antigen-1 (LFA-1) to bind on leukocytes that contribute to leukocyte adhesion at sites of inflammation. Vascular endothelial growth factor (VEGF)-A(165)b is generated by alternative splicing of VEGF-A in the terminal exon, exon 8. VEGF-A(165)b is cytoprotective and antiangiogenic, but its effects on inflammation have not yet been elucidated. Therefore, we tested the hypothesis that VEGF-A(165)b regulates TNF-α-induced ICAM-1 expression and monocyte adhesion in RPE cells.
Methods:
Primary RPE cells were pretreated with TNF-α alone, VEGF-A(165)b alone, VEGF-A(165)b with anti-VEGF-A(165)b, or the VEGFR-2 inhibitor ZM323881 before exposure to TNF-α for 24 h. Western blotting and monocyte adhesion assays were performed.
Results:
VEGF-A(165)b and ZM323881 inhibited TNF-α-induced upregulation of ICAM-1 in RPE cells. The effect of VEGF-A(165)b was neutralized by an antibody to VEGF-A(165)b. VEGF-A(165)b ameliorated TNF-α-induced monocyte-RPE adhesion.
Conclusions:
These findings indicate that VEGF-A(165)b inhibits TNF-α-mediated upregulation of ICAM-1 expression and increases monocyte-RPE cell adhesion, suggesting an anti-inflammatory property of VEGF-A(165)b in the eye.
Insights
Vascular Endothelial Growth Factor-A(165)b (VEGF-A(165)b) was found to reduce inflammation in retinal pigment epithelium (RPE) cells. It inhibits tumor necrosis factor-alpha (TNF-α)-induced ICAM-1 expression and monocyte adhesion, suggesting anti-inflammatory effects.
Area of Science:
- Ophthalmology
- Immunology
- Molecular Biology
Background:
- Local inflammation in the retinal pigment epithelium (RPE) involves inflammatory cell migration and cytokine release, such as tumor necrosis factor-alpha (TNF-α).
- TNF-α increases intercellular adhesion molecule-1 (ICAM-1) on RPE cells, facilitating leukocyte adhesion via lymphocyte function-associated antigen-1 (LFA-1).
- Vascular Endothelial Growth Factor-A(165)b (VEGF-A(165)b), an alternatively spliced form of VEGF-A, is known for cytoprotective and antiangiogenic properties, but its role in inflammation is unclear.
Purpose of the Study:
- To investigate the effect of VEGF-A(165)b on TNF-α-induced ICAM-1 expression in RPE cells.
- To determine if VEGF-A(165)b influences monocyte adhesion to RPE cells in an inflammatory context.
Main Methods:
- Primary RPE cells were treated with TNF-α, VEGF-A(165)b, an anti-VEGF-A(165)b antibody, or a VEGFR-2 inhibitor (ZM323881).
- Cells were subsequently exposed to TNF-α for 24 hours.
- Western blotting and monocyte adhesion assays were utilized to assess ICAM-1 expression and cell adhesion.
Main Results:
- VEGF-A(165)b and the VEGFR-2 inhibitor ZM323881 significantly inhibited TNF-α-induced ICAM-1 upregulation in RPE cells.
- The inhibitory effect of VEGF-A(165)b on ICAM-1 was confirmed by neutralization with a specific antibody.
- VEGF-A(165)b treatment reduced TNF-α-induced adhesion of monocytes to RPE cells.
Conclusions:
- VEGF-A(165)b demonstrates anti-inflammatory properties by inhibiting TNF-α-mediated ICAM-1 expression in RPE cells.
- VEGF-A(165)b reduces monocyte adhesion to RPE cells, further supporting its anti-inflammatory role.
- These findings suggest VEGF-A(165)b may play a protective role in ocular inflammatory conditions.
Related Concept Videos
01:31Immunoglobulin-like Cell Adhesion Molecules
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
01:17Intracellular Signaling Affects Focal Adhesions
Some...
01:24Regulation of Angiogenesis and Blood Supply