Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2008-7-16
pubmed:abstractText
Successful regeneration in the central nervous system crucially depends on the adequate environment. Microglia as brain immune-competent cells importantly contribute to this task by producing pro- and anti-inflammatory mediators. Any environmental change transforms these cells towards an activated phenotype, leading to major morphological, transcriptional and functional alterations. Rho GTPases affect multiple cellular properties, including the cytoskeleton, and C3 proteins are widely used to study their involvement. Especially C3bot from Clostridium botulinum has been considered to promote neuronal regeneration by changing Rho activity. Yet C3bot may exert cellular influences through alternative mechanisms. To determine the role of Rho-dependent pathways in microglia we investigated the influence of C3bot on functional properties of cultivated primary mouse microglial cells. Nanomolar concentrations of C3bot transformed microglia towards an activated phenotype and triggered the release of nitric oxide and several proinflammatory cyto- and chemokines. These inductions were not mediated by the ROCK-kinase pathway, since its selective inhibitors Y27632 and H1152 had no effect. C3-induced and Rho-mediated NO release was instead found to be under the control of NFkappaB, as revealed by treatment with the NFkappaB inhibitor PDTC. Thus, C3bot induces a proinflammatory response in microglia resembling the classical proinflammatory phenotype elicited by bacterial LPS. The findings are relevant for the use of C3bot in regenerative approaches.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1098-1136
pubmed:author
pubmed:copyrightInfo
(c) 2008 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1162-75
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Inhibition of Rho-dependent pathways by Clostridium botulinum C3 protein induces a proinflammatory profile in microglia.
pubmed:affiliation
Institut für Neuropathologie, Universität Göttingen, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't