Anti-Inflammatory Roles of Type I Interferon Signaling in the Lung
In this study, we investigated the role of type I interferon signaling in the inflammatory response against diverse clinically relevant stimuli. Using mice deficient in type I interferon signaling (IFNAR1-/-), we demonstrate that the absence of interferon signaling resulted in a robust and persistent inflammatory response against Pseudomonas aeruginosa, lipopolysaccharide, and chemotherapeutic agent bleomycin. The elevated inflammatory response in IFNAR1-/- mice was manifested as elevated myeloid cells such as macrophages and neutrophils, in the broncho-alveolar lavage. The inflammatory cell response in the IFNAR1-/- mice ...
Source: Am J Physiol Lung Ce... - February 20, 2024 Category: Respiratory Medicine Authors: Jingjing Feng Yi Liu Jooyoung Kim Farida Ahangari Naftali Kaminski William G Bain Zhijun Jie Charles S Dela Cruz Lokesh Sharma Source Type: research
A Novel Interaction Between Aquaporin 1 and Caspase-3 in Pulmonary Arterial Smooth Muscle Cells
Am J Physiol Lung Cell Mol Physiol. 2024 Feb 20. doi: 10.1152/ajplung.00017.2024. Online ahead of print.ABSTRACTPulmonary hypertension (PH) is a condition in which remodeling of the pulmonary vasculature leads to hypertrophy of the muscular vascular wall and extension of muscle into non-muscular arteries. These pathologic changes are predominantly due to abnormal proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), enhanced cellular functions that have been linked to increases in the cell membrane protein aquaporin-1 (AQP1). However, the mechanisms underlying increased AQP1 abundance have not bee...
Source: Am J Physiol Lung Ce... - February 20, 2024 Category: Respiratory Medicine Authors: Shannon Niedermeyer Xin Yun Marielena Trujillo Haiyang Jiang Manuella R Andrade Todd M Kolb Karthik Suresh Mahendra Damarla Larissa A Shimoda Source Type: research
Hypobaric hypoxia modulated structural characteristics of circulating cell free DNA in high altitude pulmonary edema
Am J Physiol Lung Cell Mol Physiol. 2024 Feb 13. doi: 10.1152/ajplung.00245.2023. Online ahead of print.ABSTRACTThe utility of cell free (cf) DNA has extended as a surrogate or clinical biomarker for various diseases. However, a more profound and expanded understanding of the diverse cfDNA population and its correlation with physiological phenotypes and environmental factors is imperative for utilizing its full potential. The high altitude (HA; altitude >2500 m above sea level) environment characterized by hypobaric hypoxia offers an observational case-control design to study the differential cfDNA profile in high-altit...
Source: Am J Physiol Lung Ce... - February 13, 2024 Category: Respiratory Medicine Authors: Manzoor Ali Raushni Choudhary Kanika Singh Swati Kumari Rahul Kumar Brian B Graham M A Qadar Pasha Stanzen Rabyang Tashi Thinlas Aastha Mishra Source Type: research
Decreased LPS-induced lung injury in pigs treated with a lung surfactant protein A-derived nonapeptide that inhibits peroxiredoxin 6 activity
This study addressed the efficacy of a liposome-encapsulated 9 amino acid peptide (PIP-2) for the prevention or treatment of acute lung injury (ALI) +/- sepsis. PIP-2 inhibits the PLA2 activity of peroxiredoxin 6, thereby preventing Rac release and activation of NADPH oxidases, types 1 and 2. Female Yorkshire pigs were infused intravenously with lipopolysaccharide (LPS) + liposomes (untreated) or LPS + PIP-2 encapsulated in liposomes (treated). Pigs were mechanically ventilated and continuously monitored; they were euthanized after 8 hours or earlier if pre-established humane endpoints were reached. Control pigs (mechanica...
Source: Am J Physiol Lung Ce... - February 13, 2024 Category: Respiratory Medicine Authors: Aron B Fisher Brett Zani Thomas Han Chandra Dodia Raffaele Melidone Steven Keller Source Type: research
Persistence of Emphysema Following Cessation of Cigarette Smoke Exposure Requires a Susceptibility Factor
Am J Physiol Lung Cell Mol Physiol. 2024 Feb 13. doi: 10.1152/ajplung.00342.2023. Online ahead of print.ABSTRACTChronic obstructive pulmonary disease (COPD) is caused by cigarette smoke (CS) exposure but can be often progressive even in former smokers. Exposure of mice to CS for 22 weeks causes emphysema, but whether emphysema persists after cessation of CS exposure is not clear. The purpose of this study was to determine whether emphysema persists in mice following a recovery period of 22 wks and whether a susceptibility factor, such as deficiency in the Bcl-2-interacting killer (Bik), is required for this persistence. Th...
Source: Am J Physiol Lung Ce... - February 13, 2024 Category: Respiratory Medicine Authors: Zerihun Hailemariam Nagasi Naomi Nommi Congjian Liu Yohannes Tesfaigzi Source Type: research
A preclinical systematic review and meta-analysis assessing the effect of biological sex in lipopolysaccharide-induced acute lung injury
Am J Physiol Lung Cell Mol Physiol. 2024 Feb 13. doi: 10.1152/ajplung.00336.2023. Online ahead of print.ABSTRACTIt is unclear what effect biological sex has on the outcomes of acute lung injury (ALI). Clinical studies are confounded by their observational design. We addressed this knowledge gap with a preclinical systematic review of ALI animal studies. We searched MEDLINE and Embase for studies of intratracheal/intranasal/aerosolized lipopolysaccharide (LPS) administration, the most common ALI model, and reported sex-stratified data. Screening and data extraction were conducted in duplicate. Our primary outcome was histol...
Source: Am J Physiol Lung Ce... - February 13, 2024 Category: Respiratory Medicine Authors: Eva Kuhar Nikesh Chander Duncan J Stewart Forough Jahandideh Haibo Zhang Arnold S Kristof Julie A Bastarache Eric P Schmidt Monica Taljaard Bernard Th ébaud Doreen Engelberts Dean A Fergusson Manoj M Lalu Source Type: research
Disruption of the SP-A/SP-R210 < sub > L < /sub > (Myo18A α) pathway prolongs gestation and reduces fetal survival during lipopolysaccharide-induced parturition in late gestation
We report that either lack of SP-A or disruption of SP-R210L delays parturition by 0.40 and 0.55 days compared to controls, respectively. LPS induced labor 0.60, 1.01, 0.40, 1.00, and 1.31 days earlier than PBS controls in WT, SP-A-deficient, littermate controls, heterozygous, and homozygous SP-R210L-deficient mice, respectively. Lack of SP-A reduced litter size in PBS-treated mice, whereas the total number of pups delivered was similar in all LPS-treated mice. The number of live pups, however, was significantly reduced by 50-70% in SP-A and SP-R210L-deficient mice compared to controls. Differences in gestational length we...
Source: Am J Physiol Lung Ce... - February 13, 2024 Category: Respiratory Medicine Authors: Zhiwei Guan Brandon Worth Todd M Umstead Shaili Amatya Jennifer Booth Zissis C Chroneos Source Type: research
Defining signals that promote human alveolar type I differentiation
Am J Physiol Lung Cell Mol Physiol. 2024 Feb 13. doi: 10.1152/ajplung.00191.2023. Online ahead of print.ABSTRACTAlveolar type I (ATI) cells cover >95% of the lung's distal surface and facilitate gas exchange through their exceptionally thin shape. ATI cells in vivo are replenished by alveolar type II cell division and differentiation, but a detailed understanding of ATI biology has been hampered by the challenges in direct isolation of these cell due to their fragility, and incomplete understanding of the signaling interactions that promote differentiation of ATII to ATI cells. Here we explored the signals that maintain...
Source: Am J Physiol Lung Ce... - February 13, 2024 Category: Respiratory Medicine Authors: Yong Li Y S Prakash Qi Tan Daniel J Tschumperlin Source Type: research
Myocardin regulates fibronectin expression and secretion from human pleural mesothelial cells
Am J Physiol Lung Cell Mol Physiol. 2024 Feb 13. doi: 10.1152/ajplung.00271.2023. Online ahead of print.ABSTRACTDuring the progression of pleural fibrosis, pleural mesothelial cells (PMCs) undergo a phenotype switching process known as mesothelial-mesenchymal transition (MesoMT). During MesoMT, transformed PMCs become myofibroblasts which produce increased extracellular matrix (ECM) proteins, including collagen and fibronectin (FN1) that is critical to develop fibrosis. Here, we studied the mechanism that regulates FN1 expression in myofibroblasts derived from HPMCs. We found that myocardin (Myocd), a transcriptional coact...
Source: Am J Physiol Lung Ce... - February 13, 2024 Category: Respiratory Medicine Authors: Tsuyoshi Sakai Young-Yeon Choo Shinya Mitsuhashi Reiko Ikebe Ann Jeffers Steven Idell Torry A Tucker Mitsuo Ikebe Source Type: research
Hypobaric hypoxia modulated structural characteristics of circulating cell free DNA in high altitude pulmonary edema
Am J Physiol Lung Cell Mol Physiol. 2024 Feb 13. doi: 10.1152/ajplung.00245.2023. Online ahead of print.ABSTRACTThe utility of cell free (cf) DNA has extended as a surrogate or clinical biomarker for various diseases. However, a more profound and expanded understanding of the diverse cfDNA population and its correlation with physiological phenotypes and environmental factors is imperative for utilizing its full potential. The high altitude (HA; altitude >2500 m above sea level) environment characterized by hypobaric hypoxia offers an observational case-control design to study the differential cfDNA profile in high-altit...
Source: Am J Physiol Lung Ce... - February 13, 2024 Category: Respiratory Medicine Authors: Manzoor Ali Raushni Choudhary Kanika Singh Swati Kumari Rahul Kumar Brian B Graham M A Qadar Pasha Stanzen Rabyang Tashi Thinlas Aastha Mishra Source Type: research
Decreased LPS-induced lung injury in pigs treated with a lung surfactant protein A-derived nonapeptide that inhibits peroxiredoxin 6 activity
This study addressed the efficacy of a liposome-encapsulated 9 amino acid peptide (PIP-2) for the prevention or treatment of acute lung injury (ALI) +/- sepsis. PIP-2 inhibits the PLA2 activity of peroxiredoxin 6, thereby preventing Rac release and activation of NADPH oxidases, types 1 and 2. Female Yorkshire pigs were infused intravenously with lipopolysaccharide (LPS) + liposomes (untreated) or LPS + PIP-2 encapsulated in liposomes (treated). Pigs were mechanically ventilated and continuously monitored; they were euthanized after 8 hours or earlier if pre-established humane endpoints were reached. Control pigs (mechanica...
Source: Am J Physiol Lung Ce... - February 13, 2024 Category: Respiratory Medicine Authors: Aron B Fisher Brett Zani Thomas Han Chandra Dodia Raffaele Melidone Steven Keller Source Type: research
Persistence of Emphysema Following Cessation of Cigarette Smoke Exposure Requires a Susceptibility Factor
Am J Physiol Lung Cell Mol Physiol. 2024 Feb 13. doi: 10.1152/ajplung.00342.2023. Online ahead of print.ABSTRACTChronic obstructive pulmonary disease (COPD) is caused by cigarette smoke (CS) exposure but can be often progressive even in former smokers. Exposure of mice to CS for 22 weeks causes emphysema, but whether emphysema persists after cessation of CS exposure is not clear. The purpose of this study was to determine whether emphysema persists in mice following a recovery period of 22 wks and whether a susceptibility factor, such as deficiency in the Bcl-2-interacting killer (Bik), is required for this persistence. Th...
Source: Am J Physiol Lung Ce... - February 13, 2024 Category: Respiratory Medicine Authors: Zerihun Hailemariam Nagasi Naomi Nommi Congjian Liu Yohannes Tesfaigzi Source Type: research
A preclinical systematic review and meta-analysis assessing the effect of biological sex in lipopolysaccharide-induced acute lung injury
Am J Physiol Lung Cell Mol Physiol. 2024 Feb 13. doi: 10.1152/ajplung.00336.2023. Online ahead of print.ABSTRACTIt is unclear what effect biological sex has on the outcomes of acute lung injury (ALI). Clinical studies are confounded by their observational design. We addressed this knowledge gap with a preclinical systematic review of ALI animal studies. We searched MEDLINE and Embase for studies of intratracheal/intranasal/aerosolized lipopolysaccharide (LPS) administration, the most common ALI model, and reported sex-stratified data. Screening and data extraction were conducted in duplicate. Our primary outcome was histol...
Source: Am J Physiol Lung Ce... - February 13, 2024 Category: Respiratory Medicine Authors: Eva Kuhar Nikesh Chander Duncan J Stewart Forough Jahandideh Haibo Zhang Arnold S Kristof Julie A Bastarache Eric P Schmidt Monica Taljaard Bernard Th ébaud Doreen Engelberts Dean A Fergusson Manoj M Lalu Source Type: research
Disruption of the SP-A/SP-R210 < sub > L < /sub > (Myo18A α) pathway prolongs gestation and reduces fetal survival during lipopolysaccharide-induced parturition in late gestation
We report that either lack of SP-A or disruption of SP-R210L delays parturition by 0.40 and 0.55 days compared to controls, respectively. LPS induced labor 0.60, 1.01, 0.40, 1.00, and 1.31 days earlier than PBS controls in WT, SP-A-deficient, littermate controls, heterozygous, and homozygous SP-R210L-deficient mice, respectively. Lack of SP-A reduced litter size in PBS-treated mice, whereas the total number of pups delivered was similar in all LPS-treated mice. The number of live pups, however, was significantly reduced by 50-70% in SP-A and SP-R210L-deficient mice compared to controls. Differences in gestational length we...
Source: Am J Physiol Lung Ce... - February 13, 2024 Category: Respiratory Medicine Authors: Zhiwei Guan Brandon Worth Todd M Umstead Shaili Amatya Jennifer Booth Zissis C Chroneos Source Type: research
Defining signals that promote human alveolar type I differentiation
Am J Physiol Lung Cell Mol Physiol. 2024 Feb 13. doi: 10.1152/ajplung.00191.2023. Online ahead of print.ABSTRACTAlveolar type I (ATI) cells cover >95% of the lung's distal surface and facilitate gas exchange through their exceptionally thin shape. ATI cells in vivo are replenished by alveolar type II cell division and differentiation, but a detailed understanding of ATI biology has been hampered by the challenges in direct isolation of these cell due to their fragility, and incomplete understanding of the signaling interactions that promote differentiation of ATII to ATI cells. Here we explored the signals that maintain...
Source: Am J Physiol Lung Ce... - February 13, 2024 Category: Respiratory Medicine Authors: Yong Li Y S Prakash Qi Tan Daniel J Tschumperlin Source Type: research
