α-Linolenic acid attenuates pseudo-allergic reactions by inhibiting Lyn kinase activity
Copyright © 2020. Published by Elsevier GmbH..
BACKGROUND: Pseudo-allergic reactions are potentially fatal hypersensitivity responses caused by mast cell activation. α-linolenic acid (ALA) is known for its anti-allergic properties. However, its potential anti-pseudo-allergic effects were not much investigated.
PURPOSE: To investigate the inhibitory effects of ALA on IgE-independent allergy in vitro, and in vivo, as well as the mechanism underlying its effects.
METHODS/STUDY DESIGNS: The anti-anaphylactoid activity of ALA was evaluated in passive cutaneous anaphylaxis reaction (PCA) and systemic anaphylaxis models. Calcium imaging was used to assess intracellular Ca2+ mobilization. The release of cytokines and chemokines was measured using enzyme immunoassay kits. Western blot analysis was conducted to investigate the molecules of Lyn-PLCγ-IP3R-Ca2+ and Lyn-p38/NF-κB signaling pathway.
RESULTS: ALA (0, 1.0, 2.0, and 4.0 mg/kg) dose-dependently reduced serum histamine, chemokine release, vasodilation, eosinophil infiltration, and the percentage of degranulated mast cells in C57BL/6 mice. In addition, ALA (0, 50, 100, and 200 μM) reduced Compound 48/80 (C48/80) (30 μg/ml)-or Substance P (SP) (4 μg/ml)-induced calcium influx, mast cell degranulation and cytokines and chemokine release in Laboratory of Allergic Disease 2 (LAD2) cells via Lyn-PLCγ-IP3R-Ca2+ and Lyn-p38/NF-κB signaling pathway. Moreover, ALA (0, 50, 100, and 200 μM) inhibited C48/80 (30 μg/ml)- and SP (4 μg/ml)-induced calcium influx in Mas-related G-protein coupled receptor member X2 (MrgX2)-HEK293 cells and in vitro kinase assays confirmed that ALA inhibited the activity of Lyn kinase. In response to 200 μM of ALA, the activity of Lyn kinase by (7.296 ± 0.03751) × 10-5 units/μl and decreased compared with C48/80 (30 μg/ml) by (8.572 ± 0.1365) ×10-5 units/μl.
CONCLUSION: Our results demonstrate that ALA might be a potential Lyn kinase inhibitor, which could be used to treat pseudo-allergic reaction-related diseases such as urticaria.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:80 |
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| Enthalten in: |
Phytomedicine : international journal of phytotherapy and phytopharmacology - 80(2021) vom: 01. Jan., Seite 153391 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ding, Yuanyuan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.01.2021 Date Revised 26.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.phymed.2020.153391 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a α-Linolenic acid attenuates pseudo-allergic reactions by inhibiting Lyn kinase activity |
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| 500 | |a Date Revised 26.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020. Published by Elsevier GmbH. | ||
| 520 | |a BACKGROUND: Pseudo-allergic reactions are potentially fatal hypersensitivity responses caused by mast cell activation. α-linolenic acid (ALA) is known for its anti-allergic properties. However, its potential anti-pseudo-allergic effects were not much investigated | ||
| 520 | |a PURPOSE: To investigate the inhibitory effects of ALA on IgE-independent allergy in vitro, and in vivo, as well as the mechanism underlying its effects | ||
| 520 | |a METHODS/STUDY DESIGNS: The anti-anaphylactoid activity of ALA was evaluated in passive cutaneous anaphylaxis reaction (PCA) and systemic anaphylaxis models. Calcium imaging was used to assess intracellular Ca2+ mobilization. The release of cytokines and chemokines was measured using enzyme immunoassay kits. Western blot analysis was conducted to investigate the molecules of Lyn-PLCγ-IP3R-Ca2+ and Lyn-p38/NF-κB signaling pathway | ||
| 520 | |a RESULTS: ALA (0, 1.0, 2.0, and 4.0 mg/kg) dose-dependently reduced serum histamine, chemokine release, vasodilation, eosinophil infiltration, and the percentage of degranulated mast cells in C57BL/6 mice. In addition, ALA (0, 50, 100, and 200 μM) reduced Compound 48/80 (C48/80) (30 μg/ml)-or Substance P (SP) (4 μg/ml)-induced calcium influx, mast cell degranulation and cytokines and chemokine release in Laboratory of Allergic Disease 2 (LAD2) cells via Lyn-PLCγ-IP3R-Ca2+ and Lyn-p38/NF-κB signaling pathway. Moreover, ALA (0, 50, 100, and 200 μM) inhibited C48/80 (30 μg/ml)- and SP (4 μg/ml)-induced calcium influx in Mas-related G-protein coupled receptor member X2 (MrgX2)-HEK293 cells and in vitro kinase assays confirmed that ALA inhibited the activity of Lyn kinase. In response to 200 μM of ALA, the activity of Lyn kinase by (7.296 ± 0.03751) × 10-5 units/μl and decreased compared with C48/80 (30 μg/ml) by (8.572 ± 0.1365) ×10-5 units/μl | ||
| 520 | |a CONCLUSION: Our results demonstrate that ALA might be a potential Lyn kinase inhibitor, which could be used to treat pseudo-allergic reaction-related diseases such as urticaria | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Inhibitor | |
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| 700 | 1 | |a Li, Chaomei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yongjing |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Shiling |e verfasserin |4 aut | |
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| 700 | 1 | |a Liu, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a An, Hongli |e verfasserin |4 aut | |
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