PMID- 38402021
OWN - NLM
STAT- Publisher
LR  - 20240224
IS  - 1879-0828 (Electronic)
IS  - 0953-6205 (Linking)
DP  - 2024 Feb 23
TI  - TSLP is localized in and released from human lung macrophages activated by 
      T2-high and T2-low stimuli: relevance in asthma and COPD.
LID - S0953-6205(24)00076-1 [pii]
LID - 10.1016/j.ejim.2024.02.020 [doi]
AB  - 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.
CI  - Copyright (c) 2024 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Cane, Luisa
AU  - Cane L
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy; World Allergy Organization (WAO), Center of Excellence 
      (CoE), 80131 Naples, Italy; Institute of Experimental Endocrinology and Oncology, 
      National Research Council (CNR), 80131 Naples, Italy.
FAU - Poto, Remo
AU  - Poto R
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy; World Allergy Organization (WAO), Center of Excellence 
      (CoE), 80131 Naples, Italy.
FAU - Palestra, Francesco
AU  - Palestra F
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy; World Allergy Organization (WAO), Center of Excellence 
      (CoE), 80131 Naples, Italy.
FAU - Pirozzi, Marinella
AU  - Pirozzi M
AD  - Institute of Experimental Endocrinology and Oncology, National Research Council 
      (CNR), 80131 Naples, Italy.
FAU - Parashuraman, Seetharaman
AU  - Parashuraman S
AD  - Institute of Experimental Endocrinology and Oncology, National Research Council 
      (CNR), 80131 Naples, Italy.
FAU - Iacobucci, Ilaria
AU  - Iacobucci I
AD  - CEINGE Advanced Biotechnologies, Naples, Italy; Department of Chemical Sciences, 
      University of Naples Federico II, 80126 Naples, Italy.
FAU - Ferrara, Anne Lise
AU  - Ferrara AL
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy; World Allergy Organization (WAO), Center of Excellence 
      (CoE), 80131 Naples, Italy.
FAU - La Rocca, Antonello
AU  - La Rocca A
AD  - Thoracic Surgery Unit - Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 
      Naples, Italy.
FAU - Mercadante, Edoardo
AU  - Mercadante E
AD  - Thoracic Surgery Unit - Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 
      Naples, Italy.
FAU - Pucci, Piero
AU  - Pucci P
AD  - Institute of Experimental Endocrinology and Oncology, National Research Council 
      (CNR), 80131 Naples, Italy.
FAU - Marone, Gianni
AU  - Marone G
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy; World Allergy Organization (WAO), Center of Excellence 
      (CoE), 80131 Naples, Italy; Institute of Experimental Endocrinology and Oncology, 
      National Research Council (CNR), 80131 Naples, Italy; Center for Basic and 
      Clinical Immunology Research (CISI), University of Naples Federico II, 80131 
      Naples, Italy.
FAU - Monti, Maria
AU  - Monti M
AD  - CEINGE Advanced Biotechnologies, Naples, Italy; Department of Chemical Sciences, 
      University of Naples Federico II, 80126 Naples, Italy.
FAU - Loffredo, Stefania
AU  - Loffredo S
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy; World Allergy Organization (WAO), Center of Excellence 
      (CoE), 80131 Naples, Italy; Institute of Experimental Endocrinology and Oncology, 
      National Research Council (CNR), 80131 Naples, Italy; Center for Basic and 
      Clinical Immunology Research (CISI), University of Naples Federico II, 80131 
      Naples, Italy. Electronic address: stefania.loffredo2@unina.it.
FAU - Varricchi, Gilda
AU  - Varricchi G
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy; World Allergy Organization (WAO), Center of Excellence 
      (CoE), 80131 Naples, Italy; Institute of Experimental Endocrinology and Oncology, 
      National Research Council (CNR), 80131 Naples, Italy; Center for Basic and 
      Clinical Immunology Research (CISI), University of Naples Federico II, 80131 
      Naples, Italy. Electronic address: gildanet@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20240223
PL  - Netherlands
TA  - Eur J Intern Med
JT  - European journal of internal medicine
JID - 9003220
SB  - IM
OTO - NOTNLM
OT  - Angiogenesis
OT  - Asthma
OT  - Macrophage
OT  - Mast cell
OT  - TSLP
OT  - VEGF-A
COIS- Declaration of competing interest These authors declare that they have no 
      conflicts of interests.
EDAT- 2024/02/25 00:42
MHDA- 2024/02/25 00:42
CRDT- 2024/02/24 21:54
PHST- 2024/01/08 00:00 [received]
PHST- 2024/02/05 00:00 [revised]
PHST- 2024/02/19 00:00 [accepted]
PHST- 2024/02/25 00:42 [medline]
PHST- 2024/02/25 00:42 [pubmed]
PHST- 2024/02/24 21:54 [entrez]
AID - S0953-6205(24)00076-1 [pii]
AID - 10.1016/j.ejim.2024.02.020 [doi]
PST - aheadofprint
SO  - Eur J Intern Med. 2024 Feb 23:S0953-6205(24)00076-1. doi: 
      10.1016/j.ejim.2024.02.020.