Thrombin regulates CD40 expression in microglial cells.
Microglial cells are the innate immune cells of the central nervous system and quickly respond to injury by proliferation, cytokine release, and increased cell surface antigen expression. Thrombin is a multifunctional serine proteinase, which has the capability to activate microglial cells. Here, we report that pharmaceutical-grade thrombin dose-dependently increases the expression of CD40 in N9 microglial cells. This effect is blocked by a thrombin inhibitor, mimicked by thrombin receptor-activating peptide and modified by mitogen-activated protein kinase pathway inhibitors. Thrombin-induced CD40 regulation might play a role in diseases with breakdown of the blood-brain barrier such as multiple sclerosis or stroke.
Weinstein
Jonathan R
JR
Department of Neurology, School of Medicine, University of Washington, Seattle, Washington 98195, USA. jweinste@u.washington.edu
Ettinger
Russell E
RE
Zhang
Matthew
M
Andersen
Henrik
H
Hanisch
Uwe-Karsten
UK
Möller
Thomas
T
D000818:Animals; D019013:CD40 Antigens / Q000096:biosynthesis*; D002478:Cells, Cultured; D005434:Flow Cytometry; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism*
D019013:CD40 Antigens; D013917:Thrombin