Linked Life Data

18467203

Source:http://linkedlifedata.com/resource/pubmed/id/18467203

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-6-16
pubmed:abstractText
Pro-inflammatory mediators formed by the kallikrein-kinin system can stimulate bone resorption and synergistically potentiate bone resorption induced by IL-1 and TNF-alpha. We have shown that the effect is associated with synergistically enhanced RANKL expression and enhanced prostaglandin biosynthesis, due to increased cyclooxygenase-2 expression. In the present study, the effects of osteotropic cytokines and different kinins on the expression of receptor subtypes for bradykinin (BK), des-Arg10-Lys-BK (DALBK), IL-1beta and TNF-alpha have been investigated. IL-1beta and TNF-alpha enhanced kinin B1 and B2 receptor binding in the human osteoblastic cell line MG-63 and the mRNA expression of B1 and B2 receptors in MG-63 cells, human gingival fibroblasts and intact mouse calvarial bones. Kinins did not affect mRNA expression of IL-1 or TNF receptors. EMSA showed that IL-1beta and TNF-alpha activated NF-kappaB and AP-1 in MG-63 cells. IL-1beta stimulated NF-kappaB via a non-canonical pathway (p52/p65) and TNF-alpha via the canonical pathway (p50/p65). Activation of AP-1 involved c-Jun in both IL-1beta and TNF-alpha stimulated cells, but c-Fos only in TNF-alpha stimulated cells. Phospho-ELISA and Western blots showed that IL-1beta activated JNK and p38, but not ERK 1/2 MAP kinase. Pharmacological inhibitors showed that NF-kappaB, p38 and JNK were important for IL-1beta induced stimulation of B1 receptors, and NF-kappaB and p38 for B2 receptors. p38 and JNK were important for TNF-alpha induced stimulation of B1 receptors, whereas NF-kappaB, p38 and JNK were involved in TNF-alpha induced expression of B2 receptors. These data show that IL-1beta and TNF-alpha upregulate B1 and B2 receptor expression by mechanisms involving activation of both NF-kappaB and MAP kinase pathways, but that signal transduction pathways are different for IL-1beta and TNF-alpha. The enhanced kinin receptor expression induced by the pro-inflammatory cytokines IL-1beta and TNF-alpha might be one important mechanism involved in the synergistic enhancement of prostaglandin formation caused by co-treatment with kinins and one of the two cytokines. These mechanisms might help to explain the enhanced bone resorption associated with inflammatory disorders, including periodontitis and rheumatoid arthritis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
8756-3282
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
72-83
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18467203-Base Sequence, pubmed-meshheading:18467203-Cell Line, Tumor, pubmed-meshheading:18467203-DNA Primers, pubmed-meshheading:18467203-Electrophoretic Mobility Shift Assay, pubmed-meshheading:18467203-Enzyme Activation, pubmed-meshheading:18467203-Fibroblasts, pubmed-meshheading:18467203-Humans, pubmed-meshheading:18467203-Interleukin-1, pubmed-meshheading:18467203-Mitogen-Activated Protein Kinases, pubmed-meshheading:18467203-NF-kappa B, pubmed-meshheading:18467203-Osteoblasts, pubmed-meshheading:18467203-Phosphorylation, pubmed-meshheading:18467203-Radioligand Assay, pubmed-meshheading:18467203-Receptor, Bradykinin B1, pubmed-meshheading:18467203-Receptor, Bradykinin B2, pubmed-meshheading:18467203-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18467203-Signal Transduction, pubmed-meshheading:18467203-Tumor Necrosis Factor-alpha
pubmed:year
2008
pubmed:articleTitle
Kinin B1 and B2 receptor expression in osteoblasts and fibroblasts is enhanced by interleukin-1 and tumour necrosis factor-alpha. Effects dependent on activation of NF-kappaB and MAP kinases.
pubmed:affiliation
Oral Cell Biology, Umeå University, Umeå , Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't