TSLP is localized in and released from human lung macrophages activated by T2-high and T2-low stimuli : relevance in asthma and COPD
Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
European journal of internal medicine - (2024) vom: 23. Feb. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Canè, Luisa [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Angiogenesis |
|---|
| Anmerkungen: |
Date Revised 24.02.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1016/j.ejim.2024.02.020 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368919978 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368919978 | ||
| 003 | DE-627 | ||
| 005 | 20240229152053.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240229s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ejim.2024.02.020 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1305.xml |
| 035 | |a (DE-627)NLM368919978 | ||
| 035 | |a (NLM)38402021 | ||
| 035 | |a (PII)S0953-6205(24)00076-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Canè, Luisa |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a TSLP is localized in and released from human lung macrophages activated by T2-high and T2-low stimuli |b relevance in asthma and COPD |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 24.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Angiogenesis | |
| 650 | 4 | |a Asthma | |
| 650 | 4 | |a Macrophage | |
| 650 | 4 | |a Mast cell | |
| 650 | 4 | |a TSLP | |
| 650 | 4 | |a VEGF-A | |
| 700 | 1 | |a Poto, Remo |e verfasserin |4 aut | |
| 700 | 1 | |a Palestra, Francesco |e verfasserin |4 aut | |
| 700 | 1 | |a Pirozzi, Marinella |e verfasserin |4 aut | |
| 700 | 1 | |a Parashuraman, Seetharaman |e verfasserin |4 aut | |
| 700 | 1 | |a Iacobucci, Ilaria |e verfasserin |4 aut | |
| 700 | 1 | |a Ferrara, Anne Lise |e verfasserin |4 aut | |
| 700 | 1 | |a La Rocca, Antonello |e verfasserin |4 aut | |
| 700 | 1 | |a Mercadante, Edoardo |e verfasserin |4 aut | |
| 700 | 1 | |a Pucci, Piero |e verfasserin |4 aut | |
| 700 | 1 | |a Marone, Gianni |e verfasserin |4 aut | |
| 700 | 1 | |a Monti, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Loffredo, Stefania |e verfasserin |4 aut | |
| 700 | 1 | |a Varricchi, Gilda |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of internal medicine |d 1997 |g (2024) vom: 23. Feb. |w (DE-627)NLM089689097 |x 1879-0828 |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:23 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ejim.2024.02.020 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 23 |c 02 | ||