The Causal Role of IL-4 and IL-13 in<i>Schistosoma mansoni</i>Pulmonary Hypertension

Kumar, Rahul; Mickael, Claudia; Chabon, Jacob J.; Gebreab, Liya; Rutebemberwa, Alleluiah; Garcia, Alexandra Rodriguez; Koyanagi, Daniel E.; Sanders, Linda; Gandjeva, Aneta; Kearns, Mark J.; Barthel, Lea; Janssen, William J.; Mauad, Thaís; Bandeira, Angela; Schmidt, Eric P.; Tuder, Rubin M.; Graham, Brian B.

doi:10.1164/rccm.201410-1820oc

Cited by 82 publications

(126 citation statements)

References 37 publications

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“…Schistosomiasis-induced PAH is perhaps the paradigmatic entity in which a parasite, S. mansoni, triggers a TH-2 dominant response (Graham et al 2010) and pulmonary vascular lesions identical to those seen in idiopathic PAH. Experimentally, the TH-2 inflammation leads to increased transforming growth factor (TGF)-β1 (Kumar et al 2015), which ultimately trigger pulmonary artery remodeling and PH. This process is largely dependent of thrombospondin-1 producing blood marrow monocytes (Kumar et al, unpublished).…”

Section: Pulmonary Vascular Remodeling In Phmentioning

confidence: 99%

Pulmonary vascular remodeling in pulmonary hypertension

2016

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Section: Pulmonary Vascular Remodeling In Phmentioning

confidence: 99%

Pulmonary vascular remodeling in pulmonary hypertension

2016

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“…In AIDS-associated PAH there is T lymphocyte immune insufficiency and treatment with antiviral drugs improves the PAH is some patients (28). In contrast, the schistosoma parasites lodge in the lung vessels and initially trigger a T helper 1 (TH1) immune response (29) which then switches to a T helper 2 response which is associated with the development of lung and liver lesions.…”

Section: Inflammation and Immune Response As Cause Of Pahmentioning

confidence: 99%

Challenges and opportunities in treating inflammation associated with pulmonary hypertension

Voelkel

Tamošiūnienė

Nicolls

2016

Expert Review of Cardiovascular Therapy

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Inflammatory cells are present in the lungs from patients with many, if not all, forms of severe pulmonary hypertension. Historically the first inflammatory cell identified in the pulmonary vascular lesions was the mast cell. T and B lymphocytes, as well as macrophages, are present in and around the pulmonary arterioles and many patients have elevated blood levels of interleukin 1 and 6; some patients show elevated levels of leukotriene B4. An overlap between collagen-vascular disease-associated pulmonary arterial hypertension (PAH) and idiopathic PAH exists, yet only a few studies have been designed that evaluate the effect of anti-inflammatory treatments. Here we review the pertinent data that connect PAH and inflammation/immune dysregulation and evaluate experimental models of severe PAH with an emphasis on the Sugen/athymic rat model of severe PAH. We postulate that there are more than one inflammatory phenotype and predict that there will be several anti-inflammatory treatment strategies for severe PAH.

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“…Subsequently, the local inflammatory milieu directs a shift from an M1 (inflammatory) to an aberrant M2 (reparative) phenotype, promoting deleterious vascular healing [53]. This is similar across other forms of pulmonary hypertension, where type 2 inflammation is integral to the proliferative vascular response, such as in schistosomiasis-mediated vascular disease [54]. Of relevance to this point, bone marrow-derived mononuclear cells, administered 4 weeks after monocrotaline administration, improved pulmonary hypertension through both increased VEGF expression [55] and inhibition of soluble inflammatory mediators [56].…”

Section: Pulmonary Hypertension and Myeloid Cell Disordersmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells and Pulmonary Hypertension

Bryant

Mehrad

Brusko

et al. 2018

IJMS

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Myeloid–derived suppressor cells (MDSCs) comprised a heterogeneous subset of bone marrow–derived myeloid cells, best studied in cancer research, that are increasingly implicated in the pathogenesis of pulmonary vascular remodeling and the development of pulmonary hypertension. Stem cell transplantation represents one extreme interventional strategy for ablating the myeloid compartment but poses a number of translational challenges. There remains an outstanding need for additional therapeutic targets to impact MDSC function, including the potential to alter interactions with innate and adaptive immune subsets, or alternatively, alter trafficking receptors, metabolic pathways, and transcription factor signaling with readily available and safe drugs. In this review, we summarize the current literature on the role of myeloid cells in the development of pulmonary hypertension, first in pulmonary circulation changes associated with myelodysplastic syndromes, and then by examining intrinsic myeloid cell changes that contribute to disease progression in pulmonary hypertension. We then outline several tractable targets and pathways relevant to pulmonary hypertension via MDSC regulation. Identifying these MDSC-regulated effectors is part of an ongoing effort to impact the field of pulmonary hypertension research through identification of myeloid compartment-specific therapeutic applications in the treatment of pulmonary vasculopathies.

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The Causal Role of IL-4 and IL-13 inSchistosoma mansoniPulmonary Hypertension

Cited by 82 publications

References 37 publications

Pulmonary vascular remodeling in pulmonary hypertension

Pulmonary vascular remodeling in pulmonary hypertension

Challenges and opportunities in treating inflammation associated with pulmonary hypertension

Myeloid-Derived Suppressor Cells and Pulmonary Hypertension

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