Involvement of phospholipase D in regulating expression of anti-microbial peptide human β-defensin-2

Human β-defensin expression correlates with differentiation in oral epithelium, and calcium ion, an important regulator of epithelial differentiation, plays a critical role in regulation of human β-defensin-2 (hBD-2) mRNA expression. Phospholipase D (PLD) also regulates epithelial differentiation. T...

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Bibliographic Details
Main Authors: Krisanaprakornkit S., Chotjumlong P., Kongtawelert P., Reutrakul V.
Format: Article
Language:English
Published: 2014
Online Access:http://www.scopus.com/inward/record.url?eid=2-s2.0-37549064726&partnerID=40&md5=d4053f1691c1ea02838ce91d5be4f13f
http://cmuir.cmu.ac.th/handle/6653943832/2501
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Institution: Chiang Mai University
Language: English
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Summary:Human β-defensin expression correlates with differentiation in oral epithelium, and calcium ion, an important regulator of epithelial differentiation, plays a critical role in regulation of human β-defensin-2 (hBD-2) mRNA expression. Phospholipase D (PLD) also regulates epithelial differentiation. Therefore, we examined the role of PLD in hBD-2 up-regulation by cell wall extract of Fusobacterium nucleatum and phorbol 12-myristate 13-acetate (PMA), two known hBD-2 activators. We found that hBD-2 mRNA up-regulation in human gingival epithelial cells (HGECs) by these two activators was mediated by PLD activation and blocked by ethanol and 1-butanol, PLD inhibitors. PLD activity was induced by stimulation with these two activators, and phosphatidic acid (PA), a product generated from the PLD enzymatic activity, was detected in stimulated HGECs. Dioctanoyl PA commonly used for PA induced hBD-2 mRNA expression. mRNAs for PLD1α and β splice variants as well as PLD1 protein were constitutively expressed, whereas mRNA and protein for PLD2 were expressed at much lower levels than those for PLD1. Moreover, pre-treatment with (±)-propanolol, an inhibitor of phosphatidic acid phosphohydrolases that are the downstream signaling molecules in the PLD pathway, significantly blocked hBD-2 mRNA induction by PMA in a dose-dependent manner. In conclusion, these findings indicate the involvement of PLD activation in hBD-2 up-regulation in HGECs, which correlates with the state of epithelial differentiation. © The Japanese Society for Immunology. 2007. All rights reserved.