Schwann cell locomotion during peripheral nerve inflammation

Autor: Angelika Derksen, Jan-philipp Weinberger, Sandra Labus, Mark Stettner, Anne K. Mausberg, Thomas Dehmel, Bernd C. Kieseier
Rok vydání: 2014
Předmět:
Zdroj: Journal of Neuroimmunology. 275:72
ISSN: 0165-5728
DOI: 10.1016/j.jneuroim.2014.08.189
Popis: ischemia in WT and caspase-1−/− mice. A different group of mice was treated with the specific caspase-1 inhibitor z-YVAD-FMK or control. We analyzed differential cell percentages of lymphocyte and monocyte subpopulations at 6 h and 3 days after experimental stroke by flow cytometry of blood and spleen. Serum cytokine levels were analyzed by ELISA and cellular activation after stroke detected by intracellular cytokine assays. Pyroptosis as a cause of immune cell deathwasmeasured by intracellular caspase-1 labeling and membrane disruption by 7-AAD. Results: An increase in caspase-1 activation was detected after 3 days of stroke in splenic monocytes and lymphocytes. However, caspase-1 activation in circulating leukocytes was evident only in lymphocytes but not in monocytes. Furthermore, differential blood cell counts were unaffected by caspase-1 expression after stroke. Additionally, we detected an enhanced expression of intracellular inflammatory cytokines in monocytes during the acute phase after stroke. This differential activation of caspase-1 in leukocyte subpopulations was associated with enhanced inflammatory cytokine concentrations. Genetic as well as pharmacological disruption of caspase-1 signaling abrogated leukocyte pyroptosis and the post-stroke inflammatory reaction. Conclusion: We revealed caspase-1 as a key molecule in the regulation of post-stroke immune cell death and activation. It induces early immune activation as well as delayed pyroptotic immune cell death, thereby, suggesting a novel and comprehensive molecular target to treat the complex immune dysregulation after acute brain injuries.
Databáze: OpenAIRE
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