Abstract | RATIONALE: OBJECTIVES: METHODS: Wild-type, IL-4(-/-), IL-13(-/-), and IL-4(-/-) IL-13(-/-) mice (C57BL6/J background) were intraperitoneally sensitized and intravenously challenged with S. mansoni eggs to induce experimental PH. Right ventricular catheterization was then performed, followed by quantitative analysis of the lung tissue. Lung tissue from patients with schistosomiasis-associated and connective tissue disease-associated PAH was also systematically analyzed. MEASUREMENTS AND MAIN RESULTS: CONCLUSIONS: Combined IL-4 and IL-13 deficiency is required for protection against TGF-β-induced pulmonary vascular disease after Schistosoma exposure, and targeted inhibition of this pathway is a potential novel therapeutic approach for patients with schistosomiasis-associated PAH.
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Authors | Rahul Kumar, Claudia Mickael, Jacob Chabon, Liya Gebreab, Alleluiah Rutebemberwa, Alexandra Rodriguez Garcia, Daniel E Koyanagi, Linda Sanders, Aneta Gandjeva, Mark T Kearns, Lea Barthel, William J Janssen, Thais Mauad, Angela Bandeira, Eric Schmidt, Rubin M Tuder, Brian B Graham |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 192
Issue 8
Pg. 998-1008
(Oct 15 2015)
ISSN: 1535-4970 [Electronic] United States |
PMID | 26192556
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cell Adhesion Molecules
- IL4R protein, human
- Intercellular Signaling Peptides and Proteins
- Interleukin-13
- Interleukin-4 Receptor alpha Subunit
- POSTN protein, human
- RETNLB protein, human
- STAT6 Transcription Factor
- STAT6 protein, human
- Smad2 Protein
- Smad2 protein, mouse
- Smad3 Protein
- Smad3 protein, mouse
- Stat6 protein, mouse
- Transforming Growth Factor beta
- Interleukin-4
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Topics |
- Animals
- Bone Marrow Transplantation
- Cell Adhesion Molecules
(immunology, metabolism)
- Humans
- Hypertension, Pulmonary
(etiology, immunology)
- Inflammation
- Intercellular Signaling Peptides and Proteins
(immunology, metabolism)
- Interleukin-13
(genetics, immunology)
- Interleukin-4
(genetics, immunology)
- Interleukin-4 Receptor alpha Subunit
(immunology, metabolism)
- Macrophages
(immunology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Phosphorylation
- STAT6 Transcription Factor
(immunology, metabolism)
- Schistosoma mansoni
- Schistosomiasis mansoni
(complications, immunology)
- Smad2 Protein
(immunology, metabolism)
- Smad3 Protein
(immunology, metabolism)
- Th1 Cells
(immunology)
- Th17 Cells
(immunology)
- Transforming Growth Factor beta
(immunology)
- Vascular Remodeling
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