Vitamin E down-modulates mitogen-activated protein kinases, nuclear factor-κB and inflammatory responses in lung epithelial cells

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Abstract
Summary: The airway epithelium plays an active role in acute lung inflammation by producing chemotactic factors and by expressing cell adhesion molecules involved in the migration of leucocytes to extravascular spaces. We have reported previously that neutrophil migration to airways can be down-modulated by exogenously administered vitamin E (α-tocopherol). The mechanism for this effect is not well understood, however. The action of α-tocopherol was investigated in human alveolar type II and bronchial epithelial cells stimulated with tumour necrosis factor-α. Treatment of alveolar epithelial cells with α-tocopherol resulted in down-regulated cell surface expression of intercellular adhesion molecule-1 (ICAM-1). On bronchial epithelial cells, both ICAM-1 and vascular adhesion molecule-1 were decreased, leading to diminished adherence of leucocytes to the cells. The production of the neutrophil chemoattractant interleukin-8 was attenuated in both alveolar and bronchial cells. These effects were preceded by reduced activation of the mitogen-activated protein kinases (MAPK), extracellular signal-regulated kinase (ERK1/2) and p38, as well as down-regulation of nuclear factor-κB. Comparing the effects of α-tocopherol with that of specific inhibitors of MAPK and protein kinase C (PKC) revealed that effects appear to be partly independent of PKC inhibition. These results implicate the anti-inflammatory action of α-tocopherol in addition to its anti-oxidant properties.