In:
International Archives of Allergy and Immunology, S. Karger AG, Vol. 161, No. Suppl. 2 ( 2013), p. 37-43
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 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 (FceRI) on mast cells results in rapid increases in intracellular free calcium concentration [Ca 〈 sup 〉 2+ 〈 /sup 〉 ] 〈 sub 〉 i 〈 /sub 〉 and consequent activation of many transcription factors, including NFAT, NF- & #954;B, JNK and CREB. Ca 〈 sup 〉 2+ 〈 /sup 〉 signaling is essential for many cellular activities such as proliferation, gene expression and degranulation in mast cells. In addition to Ca 〈 sup 〉 2+ 〈 /sup 〉 signaling, previous reports have shown that IkappaB kinase 2 (IKK2 or IKKß), a central component of the IKK complex mediating NF- & #954;B activation, also plays a crucial role in FceRI-mediated degranulation and cytokine production. Moreover, it has been demonstrated that activation of PKCß, a calcium-dependent PKC isoform, leads to IKK2 activation in many cell types. However, the roles of Ca 〈 sup 〉 2+ 〈 /sup 〉 signaling and PKCß in the activation of IKK2 in mast cells remain largely unknown. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 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- & #954;B-dependent gene induction, degranulation, proinflammatory cytokine production and extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation by using IKK2-deficient (IKK2 〈 sup 〉 -/- 〈 /sup 〉 ) fetal liver-derived mast cells (FLMCs). 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 A23187 activated IKK2 and NF- & #954;B even in the presence of Gö6976 in mast cells. A23187-induced degranulation, cytokine production and activation of ERK1/2 were diminished in IKK2 〈 sup 〉 -/- 〈 /sup 〉 FLMCs compared to those in wild-type FLMCs. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Ca 〈 sup 〉 2+ 〈 /sup 〉 -IKK2 signaling is involved in the degranulation and cytokine production in activated mast cells by a mechanism independent of PKCß.
Type of Medium:
Online Resource
ISSN:
1018-2438
,
1423-0097
Language:
English
Publisher:
S. Karger AG
Publication Date:
2013
detail.hit.zdb_id:
1482722-0
