RGD Reference Report - In vivo inhibition of angiogenesis by interleukin-13 gene therapy in a rat model of rheumatoid arthritis. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

In vivo inhibition of angiogenesis by interleukin-13 gene therapy in a rat model of rheumatoid arthritis.

Authors: Haas, CS  Amin, MA  Ruth, JH  Allen, BL  Ahmed, S  Pakozdi, A  Woods, JM  Shahrara, S  Koch, AE 
Citation: Haas CS, etal., Arthritis Rheum. 2007 Aug;56(8):2535-48.
RGD ID: 4889497
Pubmed: PMID:17665443   (View Abstract at PubMed)
DOI: DOI:10.1002/art.22823   (Journal Full-text)

OBJECTIVE: Interleukin-13 (IL-13) is a pleiotropic cytokine that can affect vessel formation, an important component of the rheumatoid arthritis (RA) synovial tissue pannus. The purpose of this study was to use a gene therapy approach to investigate the role of IL-13 in angiogenesis in vivo, using a rat adjuvant-induced arthritis model of RA. METHODS: Ankle joints of female rats were injected preventatively with an adenovirus vector containing human IL-13 (AxCAIL-13), a control vector with no insert (AxCANI), or phosphate buffered saline (PBS). Joints were harvested at the peak of arthritis, and histologic and biochemical features were evaluated. RESULTS: AxCAIL-13-treated joint homogenates had lower hemoglobin levels, suggesting reduced joint vascularity, and both endothelial cell migration and tube formation were significantly inhibited (P < 0.05). Similarly, AxCAIL-13 inhibited capillary sprouting in the rat aortic ring assay and vessel growth in the Matrigel plug in vivo assay. IL-13 gene delivery resulted in up-regulation and association of phosphorylated ERK-1/2 and protein kinase Calpha/betaII, suggesting a novel pathway in IL-13-mediated angiostasis. The angiostatic effect of AxCAIL-13 was associated with down-regulation of proangiogenic cytokines (IL-18, cytokine-induced neutrophil chemoattractant 1/CXCL1, lipopolysaccharide-induced CXC chemokine/CXCL5) and up-regulation of the angiogenesis inhibitor endostatin. The expression and activity of matrix metalloproteinases 2 and 9, which participate in angiogenesis, was impaired in response to IL-13 as compared with AxCANI and PBS treatment. CONCLUSION: Our findings support a role for IL-13 as an in vivo antiangiogenic factor and provide a rationale for its use in RA to control pathologic neovascularization.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Arthritis  IDA 4889497 RGD 
Experimental Arthritis  ISOIL13 (Homo sapiens)4889497; 4889497 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il13  (interleukin 13)

Genes (Mus musculus)
Il13  (interleukin 13)

Genes (Homo sapiens)
IL13  (interleukin 13)


Additional Information