Durmus, N.; Chen, W.-C.; Park, S.-H.; Marsh, L.M.; 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, 11918.
Durmus, N.; Chen, W.-C.; Park, S.-H.; Marsh, L.M.; 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, 11918.
Durmus, N.; Chen, W.-C.; Park, S.-H.; Marsh, L.M.; 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, 11918.
Durmus, N.; Chen, W.-C.; Park, S.-H.; Marsh, L.M.; 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, 11918.
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 by histology, right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM2.5, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were 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 ST2-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. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMα-/- were not different from their respective wild type controls. In BALB/c mice, RELMα was a key contributor to antigen/PM2.5 induced pulmonary vascular remodeling, RV thickening and RV cytokine responses, highlighting the significance of the genetic background. The RELMα-/- animals demonstrated significantly decreased expression of RELMβ and RELM which makes these mice comparable to a situation where human RELMα levels would be significantly modified, as humans only have one RELM molecule.
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
Subject
Medicine and Pharmacology, Pulmonary and Respiratory Medicine
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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