IL-1 beta-dependent CFTR expression

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IL-1 beta-dependent CFTR expression

Interleukin 1 (IL-1 beta) stimulates expression of the Cystic fibrosis transmembrane conductance regulator (CFTR) via Nuclear factors of kappa light polypeptide in B-cells (NF-kB). The exact signaling leading to CFTR expression is unknown. The basic pathway of NF-kB activation by IL-1 beta is mediated by TNF receptor-associated factor 6 (TRAF6). IL-1 binds to Interleukin 1 receptor type I (IL-1RI) and activates transcription factors via cytoplasmic mediators such as myeloid differentiation primary response gene (MyD88), IL-1 receptor-associated kinase (IRAK) and TRAF6 [1], [2]. These intracellular processes result in recruitment and activation of I kappa B kinases complex (IKK). IKK phosphorylates NF-KB inhibitor (I-KB) and thereby marks it for degradation, consequently leading to increase in DNA-binding activity of the NF-kB [3] that directly activates transcription of CFTR [4], [5].

References:

  1. Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K
    The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 1999 Mar 18;398(6724):252-6
  2. Akira S
    Toll-like receptor signaling. The Journal of biological chemistry 2003 Oct 3;278(40):38105-8
  3. Yamamoto Y, Gaynor RB
    IkappaB kinases: key regulators of the NF-kappaB pathway. Trends in biochemical sciences 2004 Feb;29(2):72-9
  4. Brouillard F, Bouthier M, Leclerc T, Clement A, Baudouin-Legros M, Edelman A
    NF-kappa B mediates up-regulation of CFTR gene expression in Calu-3 cells by interleukin-1beta. The Journal of biological chemistry 2001 Mar 23;276(12):9486-91
  5. Cafferata EG, Guerrico AM, Pivetta OH, Santa-Coloma TA
    NF-kappaB activation is involved in regulation of cystic fibrosis transmembrane conductance regulator (CFTR) by interleukin-1beta. The Journal of biological chemistry 2001 May 4;276(18):15441-4

  1. Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K
    The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 1999 Mar 18;398(6724):252-6
  2. Akira S
    Toll-like receptor signaling. The Journal of biological chemistry 2003 Oct 3;278(40):38105-8
  3. Yamamoto Y, Gaynor RB
    IkappaB kinases: key regulators of the NF-kappaB pathway. Trends in biochemical sciences 2004 Feb;29(2):72-9
  4. Brouillard F, Bouthier M, Leclerc T, Clement A, Baudouin-Legros M, Edelman A
    NF-kappa B mediates up-regulation of CFTR gene expression in Calu-3 cells by interleukin-1beta. The Journal of biological chemistry 2001 Mar 23;276(12):9486-91
  5. Cafferata EG, Guerrico AM, Pivetta OH, Santa-Coloma TA
    NF-kappaB activation is involved in regulation of cystic fibrosis transmembrane conductance regulator (CFTR) by interleukin-1beta. The Journal of biological chemistry 2001 May 4;276(18):15441-4

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