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: Role of calcium ionophore A23187-induced activation of IkappaB kinase 2 in mast cells.
    Author: Hosokawa J, Suzuki K, Nakagomi D, Tamachi T, Takatori H, Suto A, Nakajima H.
    Journal: Int Arch Allergy Immunol; 2013; 161 Suppl 2():37-43. PubMed ID: 23711852.
    Abstract:
    BACKGROUND: Mast cells are known to play a pivotal role in allergic diseases by releasing granules containing histamine and other preformed chemical mediators. Cross-linking of high-affinity receptors for IgE (FcεRI) on mast cells results in rapid increases in intracellular free calcium concentration [Ca(2+)]i and consequent activation of many transcription factors, including NFAT, NF-κB, JNK and CREB. Ca(2+) signaling is essential for many cellular activities such as proliferation, gene expression and degranulation in mast cells. In addition to Ca(2+) signaling, previous reports have shown that IkappaB kinase 2 (IKK2 or IKKβ), a central component of the IKK complex mediating NF-κB activation, also plays a crucial role in FcεRI-mediated degranulation and cytokine production. Moreover, it has been demonstrated that activation of PKCβ, a calcium-dependent PKC isoform, leads to IKK2 activation in many cell types. However, the roles of Ca(2+) signaling and PKCβ in the activation of IKK2 in mast cells remain largely unknown. METHODS: We investigated the effect of PKC inhibitor Gö6976 on calcium ionophore A23187-induced activation of IKK2 in mast cells. We also examined the role of IKK2 in A23187-induced NF-κB-dependent gene induction, degranulation, proinflammatory cytokine production and extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation by using IKK2-deficient (IKK2(-/-)) fetal liver-derived mast cells (FLMCs). RESULTS: A23187 activated IKK2 and NF-κB even in the presence of Gö6976 in mast cells. A23187-induced degranulation, cytokine production and activation of ERK1/2 were diminished in IKK2(-/-) FLMCs compared to those in wild-type FLMCs. CONCLUSIONS: Ca(2+)-IKK2 signaling is involved in the degranulation and cytokine production in activated mast cells by a mechanism independent of PKCβ.
    [Abstract] [Full Text] [Related] [New Search]