RGD Reference Report - Interleukin-6 receptor-mediated activation of signal transducer and activator of transcription-3 (STAT3) promotes choroidal neovascularization. - Rat Genome Database

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Interleukin-6 receptor-mediated activation of signal transducer and activator of transcription-3 (STAT3) promotes choroidal neovascularization.

Authors: Izumi-Nagai, K  Nagai, N  Ozawa, Y  Mihara, M  Ohsugi, Y  Kurihara, T  Koto, T  Satofuka, S  Inoue, M  Tsubota, K  Okano, H  Oike, Y  Ishida, S 
Citation: Izumi-Nagai K, etal., Am J Pathol. 2007 Jun;170(6):2149-58.
RGD ID: 8694307
Pubmed: PMID:17525280   (View Abstract at PubMed)
PMCID: PMC1899441   (View Article at PubMed Central)
DOI: DOI:10.2353/ajpath.2007.061018   (Journal Full-text)

Interleukin (IL)-6, a potent proinflammatory cytokine, is suggested to be a risk factor for choroidal neovascularization (CNV) because of its increased levels in the serum of patients with age-related macular degeneration; however, the role of IL-6 in CNV has not been defined. The present study reveals the critical contribution of IL-6 signaling and its downstream STAT3 pathway to the murine model of laser-induced CNV. CNV induction by laser treatment stimulated IL-6 expression in the retinal pigment epithelium-choroid complex, and antibody-based blockade of IL-6 receptor or genetic ablation of IL-6 led to significant suppression of CNV. CNV generation was accompanied by STAT3 activation in choroidal endothelial cells and macrophages, and IL-6 receptor blockade resulted in selectively inhibited phosphorylation of STAT3 but not extracellular signal-regulated kinase 1/2. Consistently, pharmacological blockade of STAT3 pathway also suppressed CNV. In addition, IL-6 receptor neutralization led to significant inhibition of the in vivo and in vitro expression of inflammation-related molecules including monocyte chemotactic protein, intercellular adhesion molecule-1, and vascular endothelial growth factor, and of macrophage infiltration into CNV. These results indicate the significant involvement of IL-6 receptor-mediated activation of STAT3 inflammatory pathway in CNV generation, suggesting the possibility of IL-6 receptor blockade as a therapeutic strategy to suppress CNV associated with age-related macular degeneration.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Choroidal Neovascularization treatmentISOStat3 (Mus musculus)8694307; 8694307 RGD 
Choroidal Neovascularization treatmentIDA 8694307 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Stat3  (signal transducer and activator of transcription 3)

Genes (Mus musculus)
Stat3  (signal transducer and activator of transcription 3)

Genes (Homo sapiens)
STAT3  (signal transducer and activator of transcription 3)


Additional Information