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The neuroprotective agents chlomethiazole and SB203580 inhibit IL-1β signalling but not its biosynthesis in rat cortical glial cells by Anastasia Simi; Margareta Porsmyr-Palmertz; Anna Hjertén; Magnus Ingelman-Sundberg; Niclas Tindberg is a Neuroscience article available to read on EtoBox.
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## Abstract Chlomethiazole and pyridinyl imidazole compounds, exemplified by SB203580, are structurally distinct p38 mitogen‐activated protein kinase inhibitors with neuroprotective properties in models of cerebral ischaemia. We have examined their effects in interleukin‐1β (IL‐1β) synthesis, release and signalling in rat cortical glial cells, given the important role of IL‐1β in cerebral ischaemia. We analysed (i) IL‐1β mRNA expression by northern blot, (ii) IL‐1β protein precursor levels within the cells by western blot, and (iii) the levels of the mature IL‐1β protein secreted into the medium by enzyme‐linked immunosorbent assay (ELISA) after treatment of rat cortical glial cells with lipopolysaccharide. While the induction of IL‐1β expression by lipopolysaccharide or by IL‐1β itself was very sensitive to nuclear factor kappa B (NF‐κB) inhibitors, chlomethiazole or SB203580 were nearly without effect, indicating a differential regulation as compared to peripheral cells, e.g. monocytes. In contrast, chlomethiazole and SB203580 potently inhibited the IL‐1β‐induced expression of c‐__fos__ and inducible nitric oxide synthase, as monitored by northern blot and quantitative RT–PCR, re
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- Author
- Anastasia Simi; Margareta Porsmyr-Palmertz; Anna Hjertén; Magnus Ingelman-Sundberg; Niclas Tindberg
- Publisher
- John Wiley and Sons; Wiley (Blackwell Publishing); Blackwell Publishing Inc.; Wiley (ISSN 0022-3042)
- Published
- 2002
- Language
- EN
- Field
- Neuroscience (Life Sciences)