These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Erythromycin inhibits transcriptional activation of NF-kappaB, but not NFAT, through calcineurin-independent signaling in T cells.
    Author: Aoki Y, Kao PN.
    Journal: Antimicrob Agents Chemother; 1999 Nov; 43(11):2678-84. PubMed ID: 10543746.
    Abstract:
    The molecular mechanism of the anti-inflammatory effect of erythromycin (EM) was investigated at the level of transcriptional regulation of cytokine gene expression in T cells. EM (>10(-6) M) significantly inhibited interleukin-8 (IL-8) expression but not IL-2 expression from T cells induced with 20 ng of phorbol 12-myristate 13-acetate (PMA) per ml plus 2 microM calcium ionophore (P-I). In electrophoretic mobility shift assays EM at 10(-7) to 10(-5) M concentrations inhibited nuclear factor kappa B (NF-kappaB) DNA-binding activities induced by P-I. Reporter gene assays also showed that EM (10(-5) M) inhibited IL-8 NF-kappaB transcription by 37%. The inhibitory effects of EM on transcriptional activation of IL-2 and DNA-binding activity of nuclear factor of activated T cells (NFAT) were not seen in T cells. On the other hand, FK506, which is also a macrolide derivative, inhibited transcriptional activation of both NF-kappaB and NFAT more strongly than EM did. The mechanism of EM inhibition of transactivation of NF-kappaB was further investigated in transiently transfected T cells that express calcineurin A and B subunits. Expression of calcineurin did not render transactivation of NF-kappaB in T cells more resistant to EM, while the inhibitory effect of FK506 on transactivation of NF-kappaB was attenuated. These findings indicate that EM is capable of inhibiting expression of the IL-8 gene in T cells through transcriptional inhibition and that this inhibition is mediated through a non-calcineurin-dependent signaling event in T lymphocytes.
    [Abstract] [Full Text] [Related] [New Search]