RGD Reference Report - Effects of IL-1beta, TNF-alpha, and macrophage migration inhibitory factor on prostacyclin synthesis in rat pulmonary artery smooth muscle cells. - Rat Genome Database

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Effects of IL-1beta, TNF-alpha, and macrophage migration inhibitory factor on prostacyclin synthesis in rat pulmonary artery smooth muscle cells.

Authors: Itoh, Akihide  Nishihira, Jun  Makita, Hironi  Miyamoto, Kenji  Yamaguchi, Etsuro  Nishimura, Masaharu 
Citation: Itoh A, etal., Respirology. 2003 Dec;8(4):467-72. doi: 10.1046/j.1440-1843.2003.00491.x.
RGD ID: 401959403
Pubmed: PMID:14629650   (View Abstract at PubMed)
DOI: DOI:10.1046/j.1440-1843.2003.00491.x   (Journal Full-text)


OBJECTIVE: Cytokines have been implicated in the pathophysiology of pulmonary hypertension. We sought to explore the possibility that prostacyclin is a link.
METHODOLOGY: We tested the effects of the cytokines interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), and macrophage migration inhibitory factor (MIF) on arachidonic acid metabolism of pulmonary artery smooth muscle cells (PASMCs) with special regard to prostacyclin (PGI2) that protects against pulmonary hypertension. Cultured rat PASMCs were treated with IL-1beta, TNF-alpha, or MIF. Expression of prostacyclin synthase (PGIS) and cyclooxygenase-2 (COX-2) mRNAs, and PGI2 synthesis, were measured.
RESULTS: We found that PGIS mRNA expression was suppressed by high concentrations of TNF-alpha and MIF, while COX-2 mRNA was induced by all three cytokines tested. IL-1beta increased PGI2 production in a dose-dependent manner. TNF-alpha and MIF also increased PGI2 production, but to a far lesser degree at high concentrations. TNF-alpha paradoxically decreased PGI2 production at a low concentration.
CONCLUSIONS: These results suggest that TNF-alpha and MIF are potentially antagonistic to the action of PGI2 in rat PASMCs via down-regulation of PGIS mRNA. Simultaneous induction of COX-2 mRNA may further counteract the action of PGI2 by increasing the levels of eicosanoids other than PGI2.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PtgisRatcellular response to tumor necrosis factor  IEP and macrophage migration inhibitory factorRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgis  (prostaglandin I2 synthase)


Additional Information