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  • 1.
    Säve, Susanne
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Mjösberg, Jenny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Poljakovic, Mirjana
    Mohlin, Camilla
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Persson, Katarina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Adenosine receptor expression in Escherichia coli-infected and cytokine-stimulated human urinary tract epithelial cells2009In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 104, no 11, p. 1758-1765Article in journal (Refereed)
    Abstract [en]

    OBJECTIVETo assess the expression and regulation of adenosine receptors in unstimulated, uropathogenic Escherichia coli (UPEC)-infected and cytokine-stimulated human urinary tract epithelial cells, and to examine the regulation of interleukin (IL)-6 secretion in response to A(2A) receptor activation.

    MATERIALS AND METHODSHuman urinary tract epithelial cells (A498, T24 and RT4) were grown in cell culture and stimulated with a mixture of pro-inflammatory cytokines (CM) or UPEC. The expression of adenosine receptors was evaluated using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunocytochemistry. IL-6 secretion was measured with an enzyme-linked immunosorbent assay.

    RESULTSRT-PCR analysis showed the presence of transcripts for the A(1), A(2A) and A(2B) receptor subtypes but not for the A(3) receptor in A498 kidney epithelial cells. The expression of A(2A) receptor mRNA increased in A498 epithelial cells exposed to CM and UPEC, while A(1) and A(2B) receptor transcripts decreased or remained unchanged. Up-regulation of A(2A) receptors was confirmed at the protein level using Western blot analysis and immunocytochemistry. There was also an increase in A(2A) receptor mRNA in human bladder epithelial cells (T24 and RT4) and in mouse bladder uroepithelium in response to cytokines and UPEC. IL-6 secretion in UPEC-infected A498 cells was decreased by 38% when exposed to the A(2A) receptor agonist CGS 21680.

    CONCLUSIONOur data showed a subtype-selective plasticity among adenosine receptors in urinary tract epithelial cells in response to UPEC-infection and cytokines. There was a consistent up-regulation of A(2A) receptors in kidney and bladder epithelial cells. Functionally, A(2A) receptor activation reduced UPEC-induced IL-6 secretion. These findings suggest that adenosine might be a previously unrecognized regulator of the mucosal response in urinary tract infection.

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