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Methylprednisolone inhibits neutrophil-endothelial cell interactions induced by interleukin-1beta under flow
N Yoshida1, T Yoshikawa, Y Nakamura
1First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Japan.
Abstract:
The effects of methylprednisolone (m-PSL) on IL-1beta-induced neutrophil-endothelial cell interactions, which are normally mediated by increased expression of both intercellular adhesion molecule-1 (ICAM-1) and E-selectin on endothelial cells, were examined using an in vitro flow system. Human neutrophilic polymorphonuclear leukocytes (PMN) were perfused at a shear stress of 1 dyne/cm2 on human umbilical vein endothelial cells (HUVEC) pretreated with IL-1beta (20 U/mL) for 4 hours. Many PMN adhered to IL-1-stimulated HUVEC and then migrated beneath endothelial cell monolayers. Treatment of HUVEC with m-PSL inhibited adherence and migration of PMN in a dose dependent manner. M-PSL also inhibited IL-1beta-induced upregulation of E-selectin and ICAM-1 on HUVEC in a dose dependent manner. These results suggest that m-PSL works as an anti-inflammatory agent through inhibiting PMN-endothelial cell interactions.
Insights
Methylprednisolone (m-PSL) reduces inflammation by inhibiting neutrophil and endothelial cell interactions. This corticosteroid decreases the expression of adhesion molecules, preventing neutrophils from adhering to and migrating through the endothelial cell layer.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Neutrophil-endothelial cell interactions are crucial in inflammatory responses.
- Intercellular adhesion molecule-1 (ICAM-1) and E-selectin mediate these interactions.
- Interleukin-1beta (IL-1beta) stimulates these adhesion molecules on endothelial cells.
Purpose of the Study:
- To investigate the anti-inflammatory effects of methylprednisolone (m-PSL).
- To examine how m-PSL affects neutrophil-endothelial cell interactions induced by IL-1beta.
- To determine the impact of m-PSL on ICAM-1 and E-selectin expression.
Main Methods:
- Utilized an in vitro flow system to study human polymorphonuclear leukocytes (PMN) and human umbilical vein endothelial cells (HUVEC).
- HUVEC were pretreated with IL-1beta to induce inflammation.
- The effects of varying doses of m-PSL on PMN adherence, migration, and adhesion molecule expression were measured.
Main Results:
- Methylprednisolone (m-PSL) significantly inhibited both neutrophil adherence and migration.
- m-PSL demonstrated a dose-dependent inhibition of PMN-endothelial cell interactions.
- The drug also dose-dependently suppressed the IL-1beta-induced upregulation of E-selectin and ICAM-1 on HUVEC.
Conclusions:
- Methylprednisolone (m-PSL) acts as an anti-inflammatory agent.
- m-PSL effectively inhibits key steps in neutrophil recruitment to inflamed sites.
- The mechanism involves downregulating adhesion molecule expression on endothelial cells, thereby reducing neutrophil-endothelial cell interactions.