Browsing by Subject "iNOS"

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    Lymph node and peri-lymph node stroma : phenotype and interaction with T-cells
    (2014-07-11) Stoffel, Nicholas J.; Touloukian, Christopher E.; Broxmeyer, Hal E.; Srour, Edward F.; Ingram Jr., David A.
    The non-hematopoietic, stationary stromal cells located inside and surrounding skin-draining lymph nodes play a key role in regulating immune responses. We studied distinct populations of lymph node stromal cells from both human subjects and animal models in order to describe their phenotype and function. In the mouse model, we studied two distinct populations: an endothelial cell population expressing Ly51 and MHC-II, and an epithelial cell population expressing the epithelial adhesion molecule EpCAM. Analysis of intra-nodal and extra-nodal lymph node (CD45-) stromal cells through flow cytometry and qPCR provides a general phenotypic profile of the distinct populations. My research focused on the EpCAM+ epithelial cell population located in the fat pad surrounding the skin draining lymph nodes. The EpCAM+ population has been characterized by surface marker phenotype, anatomic location, and gene expression profile. This population demonstrates the ability to inhibit the activation and proliferation of both CD4 and CD8 T cells. This population may play a role in suppressing overactive inflammation and auto-reactive T cells that escaped thymic deletion. The other major arm of my project consisted of identifying a novel endothelial cell population in human lymph nodes. Freshly resected lymph nodes were processed into single cell suspensions and selected for non-hematopoietic CD45- stromal cells. The unique endothelial population expressing CD34 HLA-DR was then characterized and analyzed for anatomic position, surface marker expression, and gene profiles. Overall, these studies emphasize the importance of stationary lymph node stromal cells to our functioning immune systems, and may have clinical relevance to autoimmune diseases, inflammation, and bone marrow transplantation.
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    Tephrosia purpurea, with (-)-Pseudosemiglabrin as the Major Constituent, Alleviates Severe Acute Pancreatitis-Mediated Acute Lung Injury by Modulating HMGB1 and IL-22
    (MDPI, 2025-03-13) Soliman, Gamal A.; Alamri, Mohammed A.; Abdel-Rahman, Rehab F.; Elbaset, Marawan A.; Ogaly, Hanan A.; Abdel-Kader, Maged S.; Neurology, School of Medicine
    Ischemia-reperfusion (IR) injury is a major cause of multiple organ failure. The purpose of this study was to look into the role of Tephrosia purpurea (TEP) and its active constituent pseudosemiglabrin (PS) in alleviating severe acute pancreatitis and its associated acute lung injury. We established a rat pancreatic IR model, and the rats were treated with TEP (200 mg/kg and 400 mg/kg) and PS (20 and 40 mg/kg), in addition to the IR control and sham groups. The results showed that the respiratory parameters, including inspiratory time (Ti), expiratory time (Te), duration (Dr), and respiratory rate (RR), were comparable among all groups, while peak inspiratory flow (PIF), forced vital capacity (FVC), and forced expiratory volume at 0.1 s (FEV0.1) were significantly impaired. Notably, PS at 40 mg/kg showed normal PIF, FVC, and FEV0.1/FVC compared to the IR group, indicating an improved lung function. Additionally, TEP and PS showed protective effects on pancreatic and lung tissues compared to the IR control group, with the following effects: alleviating pathological damage; reducing serum levels of trypsinogen activation peptide (TAP), lipase, and amylase; decreasing oxidative stress markers such as MDA and MPO; restoring antioxidant enzyme activity (GPx); suppressing inflammatory markers TNF-α, IL-6, and NF-κB; downregulating HMGB1 gene in pancreatic tissue; and upregulating the IL-22 gene in lung tissues. In conclusion, the obtained findings demonstrate that oral supplementation of TEP and PS to rats with pancreatic IR alleviates pancreatic and lung injuries by reducing oxidative stress and modulating inflammatory processes, which offers an attractive therapeutic option for severe acute pancreatitis and its associated acute lung injury.