Poto, Remo (2024) Role of Thymic Stromal Lymphopoietin on Inflammatory Angiogenesis and Airway Remodeling in Asthma. [Tesi di dottorato]

Documento PDF Tesi_Dottorato_Remo_Poto_Archivio_FedOA.pdf Visibile a [TBR] Amministratori dell'archivio Download (1MB) | Richiedi una copia

Abstract

Background: Macrophages are the most prevalent immune cells in the human lung, playing a pivotal role in airway inflammation such as asthma and chronic obstructive pulmonary disease (COPD). Thymic stromal lymphopoietin (TSLP), a multifunctional cytokine predominantly produced by bronchial epithelial cells, is critical in the pathobiology of asthma and COPD. TSLP exists in two forms: the long form (lfTSLP) and a shorter isoform (sfTSLP). This study aimed to determine the localization of TSLP in human lung macrophages (HLMs) and to investigate the mechanisms underlying its release from these cells. Additionally, we assessed the effects of the two TSLP variants on the release of angiogenic factors from HLMs. Methods: We used immunofluorescence and Western blot techniques to localize intracellular TSLP in HLMs isolated from human lung parenchyma. The HLMs were then activated using T2-high (IL-4, IL-13) and T2-low (lipopolysaccharide: LPS) immunological stimuli. Results: TSLP was detected in HLMs and subcellularly localized in the cytoplasm. IL-4 and LPS induced TSLP release from HLMs. Preincubation of lung macrophages with brefeldin A, which disrupts the Golgi apparatus, inhibited the release of TSLP induced by LPS and IL-4. Furthermore, lfTSLP induced the release of vascular endothelial growth factor-A (VEGF-A), a key angiogenic factor, from HLMs in a concentration-dependent manner. In contrast, sfTSLP neither activated nor interfered with the lfTSLP-induced activation of lung macrophages. Conclusions: Our findings reveal a novel immunological circuit between HLMs and TSLP. Given the crucial role of macrophages in airway inflammation, this autocrine loop could have significant translational implications, offering new insights into the pathobiology of asthma and chronic inflammatory lung diseases.

Downloads

Actions (login required)

Modifica documento