Deregulated phospholipase D2/mammalian target of rapamycin/hypoxia-inducible factor 1 alpha in peripheral T lymphocytes of oral lichen planus correlated with disease severity

Abstract

Objective: Oral lichen planus (OLP) is a common T lymphocyte-mediated autoimmune disease of unknown etiology. The mammalian target of rapamycin (mTOR) can regulate proliferation, apoptosis, and autophagy of T lymphocytes, therefore impacting the T lymphocyte-mediated immunity. The present study was aimed to investigate the possible association between Akt/mTOR/4E-BP1 (eIF4E-binding protein 1) signaling, phospholipase D (PLD) and hypoxia-inducible factor 1 alpha (Hif-1α) in peripheral T lymphocytes of OLP and the correlation of their expression with the disease severity.

Design: RAE (reticular, atrophic and erosive lesion) scores were used to assess the disease severity of OLP. Akt, mTOR, 4E-BP1, PLD1, PLD2 and Hif-1α expression in peripheral T lymphocytes were measured by using quantitative real-time polymerase chain reaction. Associations of Akt/mTOR/4E-BP1 expression with PLD1, PLD2 and Hif-1α expression were also assessed, respectively. Moreover, correlations of their expression with RAE scores were analyzed.

Results: Expressions of mTOR, 4E-BP1, PLD2 and Hif-1α mRNA were significantly reduced in peripheral T lymphocytes of OLP patients, especially in erosive form. mTOR expression was positively correlated with PLD2 and Hif-1α expression in OLP. Moreover, mTOR, PLD2 and Hif-1α expression were negatively correlated with RAE scores, respectively.

Conclusions: Deregulated PLD2/mTOR/Hif-1α may contribute to the development of OLP and reflect the severity of the disease.

Keywords: Hypoxia-inducible factor 1 alpha; Mammalian target of rapamycin; Oral lichen planus; Phospholipase D2; T lymphocyte.