Differential effects of interleukin-1 alpha and beta on interleukin-6 and chemokine synthesis in neurones.
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.
Tsakiri
Niki
N
Faculty of Life Sciences, Michael Smith Building, University of Manchester, Oxford Road, Manchester, M13 9PT, United Kingdom.
Kimber
Ian
I
Rothwell
Nancy J
NJ
Pinteaux
Emmanuel
E
D000818:Animals; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D053582:Interleukin-1alpha / Q000378:metabolism* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015213:Neuroimmunomodulation / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; C475895:Cxcl1 protein, mouse; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D019061:src-Family Kinases; D013108:Sphingomyelin Phosphodiesterase