Journal
INFLAMMATION RESEARCH
Volume 57, Issue 9, Pages 419-429Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00011-007-7213-0
Keywords
inflammatory mediators; cytokines; in vivo inflammation; intracellular signalling; NF kappa B
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Funding
- Biorebus
- Philip Morris International
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Objective and Design: We evaluated the role of the osmolarity in the pro-inflammatory responses of epithelial cells. Material: Twenty-five female Wistar rats and colorectal (HT-29) and bladder (T24) cell lines were used. Treatments: Rats and cells were exposed for 48 hours to hyperosmotic solutions. Methods: Interleukin-8 (IL-8) production was measured by Enzyme Linked ImmunoSorbent Assay, mRNA transcription of pro-inflammatory cytokines by microarrays or RNase Protection Assay. Nuclear factor-kappa B (NF-kappa B) pathway and Protein Phosphatase 2A (PP2A) activations were measured. Myeloperoxydase (MPO) activation and Macrophage-Inflammatory Protein-2 (MIP-2) transcription were monitored. Results: The exposure to hyperosmotic solutions enhanced the production of IL-8 and induced pro-inflammatory cytokines transcription. In vivo, MPO enhanced activity accompanied by an increased MIP-2 transcription was observed. In vitro, NF-kappa B activation is accompanied by an inhibitor of kappa B-alpha degradation and inhibitor of kappa B kinase (IKK gamma) activation. We demonstrated the induction of IKK gamma after methylation and activation of PP2A. Cytokine induction was inhibited by okadaic acid and calyculin A and stimulated by xylitol. Conclusion: Hyperosmolarity can induce pro-inflammatory cytokine responses in colorectal and bladder epithelial cells. Inflammation appears to be the simple consequence of a shift of methylation of PP2A which in turn activates NF-kappa B.
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