Airway Exposure to Polyethyleneimine Nanoparticles Induces Type 2 Immunity by a Mechanism Involving Oxidative Stress and ATP Release
| Autor: | Takao Kobayashi, Peter J. Maniak, Koji Iijima, Scott M. O'Grady, Noriyuki Ohkura, Hirohito Kita, Yotesawee Srisomboon |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.disease_cause
Mice chemistry.chemical_compound Adenosine Triphosphate intracellular Ca2+ allergic inflammation Polyethyleneimine Biology (General) Receptor Cells Cultured Spectroscopy Mice Inbred BALB C biology General Medicine Computer Science Applications Chemistry DIDS Cytokines Female Intracellular purinergic signaling QH301-705.5 Respiratory Mucosa macromolecular substances Article Catalysis Inorganic Chemistry Immune system medicine Animals Humans Secretion RNA Messenger Physical and Theoretical Chemistry Molecular Biology QD1-999 Organic Chemistry Immunity technology industry and agriculture Epithelial Cells Glutathione Allergens Molecular biology Oxidative Stress Ovalbumin chemistry biology.protein IL-33 Nanoparticles Calcium Th2 cytokines Oxidative stress |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 9071, p 9071 (2021) International Journal of Molecular Sciences Volume 22 Issue 16 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Polyethyleneimine (PEI) induced immune responses were investigated in human bronchial epithelial (hBE) cells and mice. PEI rapidly induced ATP release from hBE cells and pretreatment with glutathione (GSH) blocked the response. PEI activated two conductive pathways, VDAC-1 and pannexin 1, which completely accounted for ATP efflux across the plasma membrane. Moreover, PEI increased intracellular Ca2+ concentration ([Ca2+]i), which was reduced by the pannexin 1 inhibitor, 10Panx (50 μM), the VDAC-1 inhibitor, DIDS (100 μM), and was nearly abolished by pretreatment with GSH (5 mM). The increase in [Ca2+]i involved Ca2+ uptake through two pathways, one blocked by oxidized ATP (oATP, 300 μM) and another that was blocked by the TRPV-1 antagonist A784168 (100 nM). PEI stimulation also increased IL-33 mRNA expression and protein secretion. In vivo experiments showed that acute (4.5 h) PEI exposure stimulated secretion of Th2 cytokines (IL-5 and IL-13) into bronchoalveolar lavage (BAL) fluid. Conjugation of PEI with ovalbumin also induced eosinophil recruitment and secretion of IL-5 and IL-13 into BAL fluid, which was inhibited in IL-33 receptor (ST2) deficient mice. In conclusion, PEI-induced oxidative stress stimulated type 2 immune responses by activating ATP-dependent Ca2+ uptake leading to IL-33 secretion, similar to allergens derived from Alternaria. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|