Inflammation Research

, Volume 57, Issue 9, pp 419–429

Hyperosmolarity causes inflammation through the methylation of protein phosphatase 2A

  • M. Abolhassani
  • X. Wertz
  • M. Pooya
  • P. Chaumet-Riffaud
  • A. Guais
  • L. Schwartz
Article

Abstract.

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-κB) 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-κB activation is accompanied by an inhibitor of kappa B-alpha degradation and inhibitor of kappa B kinase (IKKγ) activation. We demonstrated the induction of IKKγ 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-κB.

Keywords:

Inflammatory mediators Cytokines In vivo inflammation Intracellular signalling NFκB 

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Copyright information

© Birkhaueser 2008

Authors and Affiliations

  • M. Abolhassani
    • 1
  • X. Wertz
    • 2
    • 3
  • M. Pooya
    • 1
  • P. Chaumet-Riffaud
    • 4
    • 5
  • A. Guais
    • 6
  • L. Schwartz
    • 7
  1. 1.BCG departmentPasteur Institute of IranTehranIran
  2. 2.Laboratoire d’informatiqueEcole PolytechniquePalaiseauFrance
  3. 3.Collège de FranceChaire d’Immunologie MoléculaireParisFrance
  4. 4.Univ Paris-Sud, EA4046, UFR de BicêtreLe Kremlin-BicêtreFrance
  5. 5.AP-HP, CHU de BicêtreService de Biophysique et de Médecine nucléaireLe Kremlin-BicêtreFrance
  6. 6.BiorébusParisFrance
  7. 7.Service de radiothérapie Hôpital Pitié-SalpétrièreParisFrance

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