PMID- 15784689
OWN - NLM
STAT- MEDLINE
DCOM- 20050801
LR  - 20211203
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 77
IP  - 6
DP  - 2005 Jun
TI  - Inhibition of IKK down-regulates antigen + IgE-induced TNF production by mast 
      cells: a role for the IKK-IkappaB-NF-kappaB pathway in IgE-dependent mast cell 
      activation.
PG  - 975-83
AB  - Mast cells (MC) are major effector cells for allergic diseases. Cross-linking of 
      immunoglobulin E (IgE) and its high-affinity receptor, FcepsilonRI, by antigen 
      initiates a cascade of signaling events leading to nuclear factor (NF)-kappaB 
      activation and tumor necrosis factor (TNF) production. Here, we demonstrated that 
      inhibition of inhibitor of kappaB (IkappaB) kinase (IKK) by a peptide IKK 
      inhibitor or by four individual chemical IKK inhibitors including 
      15-deoxy-prostaglandin J(2), BMS-345541, SC-514, or sulindac significantly 
      blocked IgE + trinitrophenyl (TNP)-induced TNF production by mouse bone 
      marrow-derived MC (BMMC). Moreover, IgE + TNP induced a rapid phosphorylation of 
      IKKalpha but not IKKbeta in BMMC. IgE + TNP-induced phosphorylation of IKKalpha 
      was accompanied with phosphorylation and degradation of IkappaBalpha, subsequent 
      NF-kappaB activation, and TNF production. Inhibition of IKK by sulindac decreased 
      IKKalpha phosphorylation, IkappaBalpha phosphorylation and degradation, NF-kappaB 
      activation, and TNF production by BMMC. It is interesting that IgE + TNP 
      stimulation also induced a prominent synthesis of IKKalpha and IkappaBalpha. 
      Inhibition of NF-kappaB activity by pyrrolidine dithiocarbomate (PDTC) blocked 
      IgE + TNP-induced IkappaBalpha synthesis. NF-kappaB activity and TNF production 
      were also inhibited when PDTC was used even after IgE + TNP stimulation, 
      suggesting a potential role for the newly synthesized IkappaBalpha in MC 
      activation. In addition, IgE + TNP-induced IKKalpha and IkappaBalpha 
      phosphorylation was inhibited by a protein kinase C (PKC) inhibitor Ro 31-8220. 
      Taken together, our results support a role for the IKK-IkappaB-NF-kappaB pathway, 
      which likely involves PKC in IgE-dependent TNF production by MC. Thus, IKK may 
      serve as a new target for the regulation of MC function in allergy.
FAU - Peng, Yongde
AU  - Peng Y
AD  - Department of Microbiology and Immunology, Dalhousie University, Isaac Walton 
      Killam Health Centre, Halifax, Nova Scotia, Canada.
FAU - Power, Melanie R
AU  - Power MR
FAU - Li, Bo
AU  - Li B
FAU - Lin, Tong-Jun
AU  - Lin TJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050322
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline)
RN  - 0 (Antigens)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Imidazoles)
RN  - 0 (NBD peptide, mouse)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (Peptides)
RN  - 0 (Quinoxalines)
RN  - 0 (Receptors, IgE)
RN  - 0 (Trinitrobenzenes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 184SNS8VUH (Sulindac)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (Chuk protein, mouse)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (Ikbkb protein, mouse)
RN  - EC 2.7.11.10 (Ikbke protein, mouse)
SB  - IM
MH  - Animals
MH  - Antigens/immunology
MH  - Down-Regulation
MH  - I-kappa B Kinase
MH  - I-kappa B Proteins/*antagonists & inhibitors/metabolism
MH  - Imidazoles/pharmacology
MH  - Immunoglobulin E/*immunology
MH  - Mast Cells/*immunology
MH  - Mice
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/metabolism
MH  - Peptides/pharmacology
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Quinoxalines/pharmacology
MH  - Receptors, IgE/*physiology
MH  - Sulindac/pharmacology
MH  - Trinitrobenzenes/immunology
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
EDAT- 2005/03/24 09:00
MHDA- 2005/08/02 09:00
CRDT- 2005/03/24 09:00
PHST- 2005/03/24 09:00 [pubmed]
PHST- 2005/08/02 09:00 [medline]
PHST- 2005/03/24 09:00 [entrez]
AID - jlb.0204115 [pii]
AID - 10.1189/jlb.0204115 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2005 Jun;77(6):975-83. doi: 10.1189/jlb.0204115. Epub 2005 Mar 22.