Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Durmus, N; Chen, WC; Park, SH; Marsh, LM; Kwon, S; Nolan, A; Grunig, G.
Resistin-like Molecule α and Pulmonary Vascular Remodeling: A Multi-Strain Murine Model of Antigen and Urban Ambient Particulate Matter Co-Exposure.
Int J Mol Sci. 2023; 24(15):
Doi: 10.3390/ijms241511918
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- Co-Autor*innen der Med Uni Graz
- Marsh Leigh
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- Abstract:
- Pulmonary hypertension (PH) has a high mortality and few treatment options. Adaptive immune mediators of PH in mice challenged with antigen/particulate matter (antigen/PM) has been the focus of our prior work. We identified key roles of type-2- and type-17 responses in C57BL/6 mice. Here, we focused on type-2-response-related cytokines, specifically resistin-like molecule (RELM)α, a critical mediator of hypoxia-induced PH. Because of strain differences in the immune responses to type 2 stimuli, we compared C57BL/6J and BALB/c mice. A model of intraperitoneal antigen sensitization with subsequent, intranasal challenges with antigen/PM (ovalbumin and urban ambient PM2.5) or saline was used in C57BL/6 and BALB/c wild-type or RELMα-/- mice. Vascular remodeling was assessed with histology; right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were much more prominent in the C57BL/6 strain. Compared to wild-type mice, RELMα-/- had significantly reduced pulmonary vascular remodeling in BALB/c, but not in C57BL/6 mice. RV weights, RV IL-33 and RV IL-33-receptor were significantly increased in BALB/c wild-type mice, but not in BALB/c-RELMα-/- or in C57BL/6-wild-type or C57BL/6-RELMα-/- mice in response to antigen/PM2.5. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMα-/- mice were not different from their respective wild-type controls. The RELMα-/- animals demonstrated significantly decreased expression of RELMβ and RELMγ, which makes these mice comparable to a situation where human RELMβ levels would be significantly modified, as only humans have this single RELM molecule. In BALB/c mice, RELMα was a key contributor to pulmonary vascular remodeling, increase in RV weight and RV cytokine responses induced by exposure to antigen/PM2.5, highlighting the significance of the genetic background for the biological role of RELMα.
- Find related publications in this database (using NLM MeSH Indexing)
- Mice - administration & dosage
- Humans - administration & dosage
- Animals - administration & dosage
- Interleukin-33 - administration & dosage
- Particulate Matter - toxicity
- Vascular Remodeling - administration & dosage
- Resistin - administration & dosage
- Disease Models, Animal - administration & dosage
- Intercellular Signaling Peptides and Proteins - administration & dosage
- Mice, Inbred C57BL - administration & dosage
- Hypertension, Pulmonary - metabolism
- Cytokines - administration & dosage
- Allergens - administration & dosage
- Find related publications in this database (Keywords)
- resistin-like molecule
- pulmonary hypertension
- type 2 inflammation
- adaptive immune response
- retnla
- retnlb
- retnlg
- mouse strains
- experimental pulmonary hypertension
- urban PM
- urban fine dust
- immune response in pulmonary hypertension