Coccomyxa subellipsoidea KJ Components Enhance the Expression of Metallothioneins and Th17 Cytokines during Human T Cell Activation

Author:

Seki Toshiro1ORCID,Ohshima Shino2,Komatsu Satoko3,Yamada Soga2,Kashiwagi Hirofumi4,Goto Yumiko4,Tsuda Banri5,Kanno Akiko3,Yasuda Atsushi1,Kuno Hitoshi3,Tsuji Noriko M678,Shiina Takashi29ORCID,Kametani Yoshie29ORCID

Affiliation:

1. Department of Internal Medicine, Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara 259-1193, Japan

2. Department of Molecular Life Science, Division of Basic Medical Science, Tokai University School of Medicine, Isehara 259-1193, Japan

3. DENSO CORPORATION, Kariya 448-0029, Japan

4. Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara 259-1193, Japan

5. Department of Palliative Medicine, Tokai University School of Medicine, Isehara 259-1193, Japan

6. Division of Immune Homeostasis, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 113-8602, Japan

7. Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 113-8602, Japan

8. Department of Food Science, Jumonji University, Niiza 352-8510, Japan

9. Institute of Advanced Biosciences, Tokai University, Hiratsuka 259-1207, Japan

Abstract

Coccomyxa subellipsoidea KJ (C-KJ) is a green alga with unique immunoregulatory characteristics. Here, we investigated the mechanism underlying the modification of T cell function by C-KJ components. The water-soluble extract of C-KJ was fractionated into protein (P) and sugar (S) fractions acidic (AS), basic (BS), and neutral (NS). These fractions were used for the treatment of peripheral blood mononuclear cells stimulated with toxic shock syndrome toxin-1. Transcriptome analysis revealed that both P and AS enhanced the expression of the genes encoding metallothionein (MT) family proteins, inflammatory factors, and T helper (Th) 17 cytokine and suppressed that of those encoding Th2 cytokines in stimulated T cells. The kinetics of MT1 and MT2A gene expression showed a transient increase in MT1 and maintenance of MT2A mRNA after T cell stimulation in the presence of AS. The kinetics of Th17-related cytokine secretion in the early period were comparable to those of MT2A mRNA. Furthermore, our findings revealed that static, a STAT-3 inhibitor, significantly suppressed MT2A gene expression. These findings suggest that the expression of MTs is involved in the immune regulatory function of C-KJ components, which is partially regulated by Th17 responses, and may help develop innovative immunoregulatory drugs or functional foods.

Funder

Denso CORPORATION

Publisher

MDPI AG

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