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Publication : Differential effects of interleukin-1 alpha and beta on interleukin-6 and chemokine synthesis in neurones.

First Author  Tsakiri N Year  2008
Journal  Mol Cell Neurosci Volume  38
Issue  2 Pages  259-65
PubMed ID  18434191 Mgi Jnum  J:136912
Mgi Id  MGI:3797333 Doi  10.1016/j.mcn.2008.02.015
Citation  Tsakiri N, et al. (2008) Differential effects of interleukin-1 alpha and beta on interleukin-6 and chemokine synthesis in neurones. Mol Cell Neurosci 38(2):259-65
abstractText  Interleukin (IL)-1 is a key mediator of neuroinflammation via actions of two agonists IL-1alpha and beta that bind to the IL-1 type I receptor (IL-1RI), and are thought to trigger identical responses. However, evidence suggests that IL-1alpha and beta may have differential actions in the central nervous system (CNS). The objective of this study was to test the hypothesis that IL-1alpha and beta differentially regulate the expression of IL-6 and chemokines KC, IP-10 and MCP-1 in primary neurones. Here we demonstrate that, whilst IL-1beta induced significant synthesis of IL-6 in neurones, IL-1alpha had no effect. In contrast, IL-1alpha and beta 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-1beta-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-1alpha- and IL-1beta-induced chemokines synthesis, suggesting the existence of alternative signalling pathway(s) in neurones.
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