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Flos Magnoliae and its Constituent Linoleic Acid Suppress T Lymphocyte Activation via Store-Operated Calcium Entry.

Authors
  • Kim, Hyun Jong1, 2
  • Woo, JooHan1, 2
  • Nam, Yu Ran1, 2
  • Nam, Joo Hyun1, 2
  • Kim, Woo Kyung2, 3
  • 1 Department of Physiology, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Republic of Korea. , (North Korea)
  • 2 Channelopathy Research Center (CRC), Dongguk University College of Medicine, 32 Dongguk-ro, Ilsan Dong-gu, Goyang, Gyeonggi-do 10326, Republic of Korea. , (North Korea)
  • 3 Department of Internal Medicine Graduate School of Medicine, Dongguk University, 27 Dongguk-ro, Ilsan Dong-gu, Goyang, Gyeonggi-do 10326, Republic of Korea. , (North Korea)
Type
Published Article
Journal
The American journal of Chinese medicine
Publication Date
Jan 01, 2019
Volume
47
Issue
7
Pages
1627–1641
Identifiers
DOI: 10.1142/S0192415X19500836
PMID: 31659911
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Intracellular calcium signaling is crucial for type 2 helper T cell and mast cell activation, which is essential for allergic inflammation. It is initiated by antigen-mediated receptor stimulation that triggers store-operated calcium entry (SOCE) via ORAI1 calcium channel. Flos Magnoliae (FM) is widely used to treat allergic diseases such as allergic rhinitis and asthma. Although many studies have reported that FM regulates intracellular calcium signaling, research on the exact type of calcium channel modulated by FM is scarce. Therefore, we hypothesized that the anti-allergic effects of FM might result from ORAI1 inhibition in T cells. We investigated whether a 70% ethanolic extract of FM (FMEtOH) and its constituents inhibit ORAI1 channel activity and subsequent T cell activation. We performed conventional whole-cell patch clamp studies in hSTIM1 and hORAI1-overexpressing HEK293T cells (HEKORAI1). Intracellular calcium concentration was determined using Fura-2 dye and cytokine production measurement in Jurkat T lymphocytes. FMEtOH (0.03 mg/mL) and its fractions, especially hexane fraction (FMHex, 0.01 mg/mL), significantly inhibited SOCE and IL-2 cytokine production in Jurkat T lymphocytes. GC/MS analysis showed linoleic acid (LA) as the major component of FMHex. FMHex at 0.01 mg/mL (equivalent to 10 μM LA) inhibited not only SOCE but also IL-2 production, as well as CD3/CD28 receptor co-stimulation induced calcium signaling in Jurkat T lymphocytes. FMEtOH and LA suppressed CD4+ T lymphocyte activation, at least in part, by inhibiting ISOCE. Thus, ISOCE inhibition may be a potential strategy to inhibit immune responses in inflammation.

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