Background: Macrophages are the predominant immune cells in the human lung and play a central role in airway inflammation, including asthma and chronic obstructive pulmonary disease (COPD). Thymic stromal lymphopoietin (TSLP), a pleiotropic cytokine mainly expressed by bronchial epithelial cells, plays a key role in asthma and COPD pathobiology. TSLP exists in two variants: the long form (lfTSLP) and a shorter TSLP isoform (sfTSLP). We aimed to localize TSLP in human lung macrophages (HLMs) and investigate the mechanisms of its release from these cells. We also evaluated the effects of the two variants of TSLP on the release of angiogenic factor from HLMs. Methods: We employed immunofluorescence and Western blot to localize intracellular TSLP in HLMs purified from human lung parenchyma. HLMs were activated by 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 macrophages with brefeldin A, known to disrupt the Golgi apparatus, inhibited TSLP release induced by LPS and IL-4. lfTSLP concentration-dependently induced the release of vascular endothelial growth factor-A (VEGF-A), the most potent angiogenic factor, from HLMs. sfTSLP neither activated nor interfered with the activating property of lfTSLP on macrophages. Conclusions: Our results highlight a novel immunologic circuit between HLMs and TSLP. Given the central role of macrophages in airway inflammation, this autocrine loop holds potential translational relevance in understanding innovative aspects of the pathobiology of asthma and chronic inflammatory lung disorders.

TSLP is localized in and released from human lung macrophages activated by T2-high and T2-low stimuli: relevance in asthma and COPD / Canè, Luisa; Poto, Remo; Palestra, Francesco; Pirozzi, Marinella; Parashuraman, Seetharaman; Iacobucci, Ilaria; Ferrara, Anne Lise; La Rocca, Antonello; Mercadante, Edoardo; Pucci, Piero; Marone, Gianni; Monti, Maria; Loffredo, Stefania; Varricchi, Gilda. - In: EUROPEAN JOURNAL OF INTERNAL MEDICINE. - ISSN 1879-0828. - (2024). [10.1016/j.ejim.2024.02.020]

TSLP is localized in and released from human lung macrophages activated by T2-high and T2-low stimuli: relevance in asthma and COPD

Canè, Luisa;Poto, Remo;Palestra, Francesco;Pirozzi, Marinella;Iacobucci, Ilaria;Ferrara, Anne Lise;Pucci, Piero;Marone, Gianni;Monti, Maria;Loffredo, Stefania
;
Varricchi, Gilda
2024

Abstract

Background: Macrophages are the predominant immune cells in the human lung and play a central role in airway inflammation, including asthma and chronic obstructive pulmonary disease (COPD). Thymic stromal lymphopoietin (TSLP), a pleiotropic cytokine mainly expressed by bronchial epithelial cells, plays a key role in asthma and COPD pathobiology. TSLP exists in two variants: the long form (lfTSLP) and a shorter TSLP isoform (sfTSLP). We aimed to localize TSLP in human lung macrophages (HLMs) and investigate the mechanisms of its release from these cells. We also evaluated the effects of the two variants of TSLP on the release of angiogenic factor from HLMs. Methods: We employed immunofluorescence and Western blot to localize intracellular TSLP in HLMs purified from human lung parenchyma. HLMs were activated by 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 macrophages with brefeldin A, known to disrupt the Golgi apparatus, inhibited TSLP release induced by LPS and IL-4. lfTSLP concentration-dependently induced the release of vascular endothelial growth factor-A (VEGF-A), the most potent angiogenic factor, from HLMs. sfTSLP neither activated nor interfered with the activating property of lfTSLP on macrophages. Conclusions: Our results highlight a novel immunologic circuit between HLMs and TSLP. Given the central role of macrophages in airway inflammation, this autocrine loop holds potential translational relevance in understanding innovative aspects of the pathobiology of asthma and chronic inflammatory lung disorders.
2024
TSLP is localized in and released from human lung macrophages activated by T2-high and T2-low stimuli: relevance in asthma and COPD / Canè, Luisa; Poto, Remo; Palestra, Francesco; Pirozzi, Marinella; Parashuraman, Seetharaman; Iacobucci, Ilaria; Ferrara, Anne Lise; La Rocca, Antonello; Mercadante, Edoardo; Pucci, Piero; Marone, Gianni; Monti, Maria; Loffredo, Stefania; Varricchi, Gilda. - In: EUROPEAN JOURNAL OF INTERNAL MEDICINE. - ISSN 1879-0828. - (2024). [10.1016/j.ejim.2024.02.020]
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0953620524000761-main.pdf

solo utenti autorizzati

Descrizione: PUBBLICAZIONE IN PDF
Tipologia: Versione Editoriale (PDF)
Licenza: Non specificato
Dimensione 4.16 MB
Formato Adobe PDF
4.16 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/955106
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 7
social impact