Stroke causes neuronal necrosis and generates inflammation. Pro-inflammatory molecules intervene in this process by triggering glial cell activation and leucocyte infiltration to the injured tissue. Cytokines are major mediators of the inflammatory response. Pro-inflammatory and anti-inflammatory cytokines are released in the ischaemic brain. Anti-inflammatory cytokines, such as interleukin-10, promote cell survival, whereas pro-inflammatory cytokines, such as TNFα (tumour necrosis factor α), can induce cell death. However, deleterious effects of certain cytokines can turn to beneficial actions, depending on particular features such as the concentration, time point and the very intricate network of intracellular signals that become activated and interact. A key player in the intracellular response to cytokines is the JAK (Janus kinase)/STAT (signal transducer and activator of transcription) pathway that induces alterations in the pattern of gene transcription. These changes are associated either with cell death or survival depending, among other things, on the specific proteins involved. STAT1 activation is related to cell death, whereas STAT3 activation is often associated with survival. Yet, it is clear that STAT activation must be tightly controlled, and for this reason the function of JAK/STAT modulators, such as SOCS (suppressors of cytokine signalling) and PIAS (protein inhibitor of activated STAT), and phosphatases is most relevant. Besides local effects in the ischaemic brain, cytokines are released to the circulation and affect the immune system. Unbalanced pro-inflammatory and anti-inflammatory plasma cytokine concentrations favouring an ‘anti-inflammatory’ state can decrease the immune response. Robust evidence now supports that stroke can induce an immunodepression syndrome, increasing the risk of infection. The contribution of individual cytokines and their intracellular signalling pathways to this response needs to be further investigated.
Skip Nav Destination
Article navigation
December 2006
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
October 25 2006
Signalling pathways mediating inflammatory responses in brain ischaemia
A.M. Planas;
A.M. Planas
1
*Department of Pharmacology and Toxicology, IIBB (Institute for Biomedical Research)–CSIC (Spanish Research Council), IDIBAPS (Institute of Biomedical Investigation ‘August Pi i Sunyer’), Rosselló 161, planta 6, E-08036 Barcelona, Spain
1To whom correspondence should be addressed (email ampfat@iibb.csic.es).
Search for other works by this author on:
R. Gorina;
R. Gorina
*Department of Pharmacology and Toxicology, IIBB (Institute for Biomedical Research)–CSIC (Spanish Research Council), IDIBAPS (Institute of Biomedical Investigation ‘August Pi i Sunyer’), Rosselló 161, planta 6, E-08036 Barcelona, Spain
Search for other works by this author on:
Á. Chamorro
Á. Chamorro
†Stroke Unit, Neurology Service, Hospital Clinic, IDIBAPS, Rosselló 161, planta 6, E-08036 Barcelona, Spain
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
July 25 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (6): 1267–1270.
Article history
Received:
July 25 2006
Citation
A.M. Planas, R. Gorina, Á. Chamorro; Signalling pathways mediating inflammatory responses in brain ischaemia. Biochem Soc Trans 1 December 2006; 34 (6): 1267–1270. doi: https://doi.org/10.1042/BST0341267
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.