RGD Reference Report - Angiotensin II upregulates Toll-like receptor 4 and enhances lipopolysaccharide-induced CD40 expression in rat peritoneal mesothelial cells. - Rat Genome Database

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Angiotensin II upregulates Toll-like receptor 4 and enhances lipopolysaccharide-induced CD40 expression in rat peritoneal mesothelial cells.

Authors: Wu, J  Yang, X  Zhang, YF  Zhou, SF  Zhang, R  Dong, XQ  Fan, JJ  Liu, M  Yu, XQ 
Citation: Wu J, etal., Inflamm Res. 2009 Aug;58(8):473-82. Epub 2009 Mar 7.
RGD ID: 5491178
Pubmed: PMID:19271152   (View Abstract at PubMed)
DOI: DOI:10.1007/s00011-009-0012-z   (Journal Full-text)

OBJECTIVE: Activation of Toll-like receptor 4 (TLR4) in peritoneal mesothelial cells by endotoxin contributes to peritoneal inflammation and fibrosis. Here we investigated TLR4 expression induced by angiotensin II (Ang II) and functional consequences of nuclear factor-kappaB (NF-kappaB) activation and CD40 expression in rat peritoneal mesothelial cells (RPMCs). METHODS: TLR4, CD40, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were determined by reverse transcription polymerase chain reaction (RT-PCR) and TLR4, IkappaBalpha, phospho-IkappaBalpha, NF-kappaB p65, and phospho-NF-kappaB p65 were analyzed by Western blot. The intracellular distribution of NF-kappaB p65 was detected by immunofluorescence. RESULTS: Treatment of RPMCs with Ang II resulted in an increase in the expression of TLR4 mRNA and protein levels. Preincubation of RPMCs with Ang II significantly increased lipopolysaccharide (LPS)-induced phospho-IkappaBalpha and phospho-NF-kappaB p65 protein (P < 0.05 vs. LPS alone) and CD40, TNF-alpha, and IL-6 mRNA levels (P < 0.05 vs. LPS alone). A significantly increased nuclear staining of NF-kappaB p65 in cells treated with Ang II plus LPS was also observed. CONCLUSIONS: Ang II upregulates the expression of TLR4 by RPMCs, resulting in enhanced NF-kappaB signaling and induction of CD40, TNF-alpha, and IL-6 expression. Locally produced Ang II in the peritoneum may have an amplified role in LPS-induced peritoneal inflammation.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to lipopolysaccharide  IEP 5491178 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd40  (CD40 molecule)


Additional Information