uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Protective Role of IL-6 in Vascular Remodeling in Schistosoma Pulmonary Hypertension
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Show others and affiliations
2013 (English)In: American Journal of Respiratory Cell and Molecular Biology, ISSN 1044-1549, E-ISSN 1535-4989, Vol. 49, no 6, 951-959 p.Article in journal (Refereed) Published
Abstract [en]

Schistosomiasis is one of the most common causes of pulmonary arterial hypertension worldwide, but the pathogenic mechanism by which the host inflammatory response contributes to vascular remodeling is unknown. We sought to identify signaling pathways that play protective or pathogenic roles in experimental Schistosoma-induced pulmonary vascular disease via whole-lung transcriptome analysis. Wild-type mice were experimentally exposed to Schistosoma mansoni ova by intraperitoneal sensitization followed by tail-vein augmentation, and the phenotype was assessed by right ventricular catheterization and tissue histology, as well as RNA and protein analysis. Whole-lung transcriptome analysis by microarray and RNA sequencing was performed, and RNA sequencing was analyzed according to two bioinformatics methods. Functional testing of the candidate IL-6 pathway was determined using IL-6 knockout mice and the signal transducers and activators of transcription protein-3 (STAT3) inhibitor S3I-201. Wild-type mice exposed to S. mansoni demonstrated increased right ventricular systolic pressure and thickness of the pulmonary vascular media. Whole-lung transcriptome analysis determined that the IL-6-STAT3-nuclear factor of activated T cells c2(NFATc2) pathway was up-regulated, as confirmed by PCR and the immunostaining of lung tissue from S. mansoni-exposed mice and patients who died of the disease. Mice lacking IL-6 or treated with S3I-201 developed pulmonary hypertension, associated with significant intima remodeling after exposure to S. mansoni. Whole-lung transcriptome analysis identified the up-regulation of the IL-6-STAT3-NFATc2 pathway, and IL-6 signaling was found to be protective against Schistosoma-induced intimal remodeling.

Place, publisher, year, edition, pages
2013. Vol. 49, no 6, 951-959 p.
Keyword [en]
pulmonary hypertension, schistosomiasis, gene expression profiling, IL-6
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-214025DOI: 10.1165/rcmb.2012-0532OCISI: 000328261800009OAI: oai:DiVA.org:uu-214025DiVA: diva2:684206
Available from: 2014-01-07 Created: 2014-01-07 Last updated: 2014-01-07Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Kolosionek, Ewa
By organisation
Department of Medical Biochemistry and Microbiology
In the same journal
American Journal of Respiratory Cell and Molecular Biology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 271 hits
ReferencesLink to record
Permanent link

Direct link