Linked Life Data

19356729

Source:http://linkedlifedata.com/resource/pubmed/id/19356729

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2009-5-20
pubmed:abstractText
The role of celastrol, a triterpene extracted from the Chinese "Thunder of God Vine," in allergic inflammation was investigated. Celastrol decreased the secretion of beta-hexosaminidase, decreased the release of histamine, decreased the expression of Th2 cytokines and decreased calcium influx and cell adhesion in antigen-stimulated RBL2H3 cells. Exposure to celastrol decreased the phosphorylation of extracellular regulated kinase (ERK) and the ERK kinase activity was decreased in RBL2H3 cells. A molecular dynamics simulation showed binding of celastrol to a large pocket in ERK2, which serves as the ATP-binding site. Exposure to celastrol inhibited the interaction between immunoglobulin Fc epsilon receptor I (FcepsilonRIgamma) and ERK and inhibited interaction between FcepsilonRIgamma and protein kinase C delta (PKCdelta). Antigen stimulation induced an interaction between Rac1 and ERK as well as an interaction between Rac1 and PKCdelta. Inhibition of ERK decreased Rac1 activity and inhibition of Rac1 decreased ERK activity in antigen-stimulated RBL2H3 cells. Celastrol regulated the expression of epithelial-mesenchymal transition (EMT)-related proteins through inhibition of PKCalpha, PKCdelta, and Rac1 in antigen-stimulated RBL2H3 cells. Exposure to celatrol inhibited PKCdelta activity in antigen-stimulated RBL2H3 cells. Celastrol exerted a negative effect on FcepsilonRIbeta signaling by inhibiting the interaction between heat shock protein 90 (hsp90) and proteins, such as, FcepsilonRIbeta, Akt and PKCalpha. Celastrol exerted a negative effect on in vivo atopic dermatitis induced by 2, 4-dinitrofluorobenzene (DNFB), which requires ERK. Celastrol also showed an inhibitory effect on skin inflammation induced by phorbol myristate acetate (PMA) in Balb/c mice. In summary, celastrol binds to ERK and inhibits FcepsilonRI signaling to exert an anti-inflammatory effect.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1879-0712
pubmed:author
pubmed:issnType
Electronic
pubmed:day
10
pubmed:volume
612
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
131-42
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19356729-Animals, pubmed-meshheading:19356729-Anti-Allergic Agents, pubmed-meshheading:19356729-Calcium, pubmed-meshheading:19356729-Cell Adhesion, pubmed-meshheading:19356729-Cell Line, Tumor, pubmed-meshheading:19356729-Dose-Response Relationship, Drug, pubmed-meshheading:19356729-Enzyme Activation, pubmed-meshheading:19356729-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:19356729-Female, pubmed-meshheading:19356729-Histamine Release, pubmed-meshheading:19356729-Mice, pubmed-meshheading:19356729-Mice, Inbred BALB C, pubmed-meshheading:19356729-Mice, Inbred Strains, pubmed-meshheading:19356729-Rats, pubmed-meshheading:19356729-Receptors, IgE, pubmed-meshheading:19356729-Signal Transduction, pubmed-meshheading:19356729-Specific Pathogen-Free Organisms, pubmed-meshheading:19356729-Triterpenes, pubmed-meshheading:19356729-beta-N-Acetylhexosaminidases
pubmed:year
2009
pubmed:articleTitle
Celastrol binds to ERK and inhibits FcepsilonRI signaling to exert an anti-allergic effect.
pubmed:affiliation
School of Biological Sciences, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't