TY - JOUR
T1 - Differential effects of interleukin-1 alpha and beta on interleukin-6 and chemokine synthesis in neurones
AU - Tsakiri, Niki
AU - Kimber, Ian
AU - Rothwell, Nancy J.
AU - Pinteaux, Emmanuel
N1 - , Medical Research Council, United Kingdom
PY - 2008/6
Y1 - 2008/6
N2 - Interleukin (IL)-1 is a key mediator of neuroinflammation via actions of two agonists IL-1α and β that bind to the IL-1 type I receptor (IL-1RI), and are thought to trigger identical responses. However, evidence suggests that IL-1α and β may have differential actions in the central nervous system (CNS). The objective of this study was to test the hypothesis that IL-1α and β differentially regulate the expression of IL-6 and chemokines KC, IP-10 and MCP-1 in primary neurones. Here we demonstrate that, whilst IL-1β induced significant synthesis of IL-6 in neurones, IL-1α had no effect. In contrast, IL-1α and β induced strong synthesis and constitutive release of chemokines KC, IP-10 and MCP-1 from neurones, and these responses were IL-1RI-dependent. Whilst IL-1β-induced IL-6 synthesis was dependent on the nSMase/Src kinase signalling cascade, specific inhibitors of nSMase (3-OMS) and Src kinase (PP2) failed to inhibit IL-1α- and IL-1β-induced chemokines synthesis, suggesting the existence of alternative signalling pathway(s) in neurones. © 2008 Elsevier Inc. All rights reserved.
AB - Interleukin (IL)-1 is a key mediator of neuroinflammation via actions of two agonists IL-1α and β that bind to the IL-1 type I receptor (IL-1RI), and are thought to trigger identical responses. However, evidence suggests that IL-1α and β may have differential actions in the central nervous system (CNS). The objective of this study was to test the hypothesis that IL-1α and β differentially regulate the expression of IL-6 and chemokines KC, IP-10 and MCP-1 in primary neurones. Here we demonstrate that, whilst IL-1β induced significant synthesis of IL-6 in neurones, IL-1α had no effect. In contrast, IL-1α and β induced strong synthesis and constitutive release of chemokines KC, IP-10 and MCP-1 from neurones, and these responses were IL-1RI-dependent. Whilst IL-1β-induced IL-6 synthesis was dependent on the nSMase/Src kinase signalling cascade, specific inhibitors of nSMase (3-OMS) and Src kinase (PP2) failed to inhibit IL-1α- and IL-1β-induced chemokines synthesis, suggesting the existence of alternative signalling pathway(s) in neurones. © 2008 Elsevier Inc. All rights reserved.
U2 - 10.1016/j.mcn.2008.02.015
DO - 10.1016/j.mcn.2008.02.015
M3 - Article
C2 - 18434191
SN - 1095-9327
VL - 38
SP - 259
EP - 265
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 2
ER -