Regulation of Lymphotoxin-β by Tumor Necrosis Factor, Phorbol Myristate Acetate, and Ionomycin in Jurkat T Cells

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Abstract
Lymphotoxin-β (LT- β) is a tumor necrosis factor (TNF)-related membrane-bound cytokine that forms a heterotrimeric surface lymphotoxin (LT) complex with LT-α on the surface of lymphoid cells. Although knockout studies have revealed a role in lymph node biogenesis during development, the regulation and function of surface LT in mature cell types are poorly understood. The present study aims to understand the physiologic signals that regulate the components of surface LT in Jurkat T cells. We show that the previously observed upregulation of surface LT by phorbol myristate acetate (PMA) is markedly abrogated by cotreatment with ionomycin through posttranscriptional mechanisms. In addition, the observation of striking similarities between the mRNA accumulation kinetics of LT-α and LT-β during these treatments indicates tight coupling of expression under certain conditions. In investigating the reported upregulation of LT-β during inflammation, we tested the effects of various proinflammatory and anti-inflammatory cytokines on LT-β expression. Our data demonstrate an upregulation of LT-β mRNA by the inflammatory cytokines TNF and LT-α.