RETRACTED: Sphingosine kinase 1 regulates pro-inflammatory responses triggered by TNFα in primary human monocytes (Retracted article. See vol. 227, pg. 2974, 2012)

Monocytes play an important role in inflammation, angiogenesis, and atherosclerosis. During these processes monocytes release pre-formed proinflammatory mediators from granules, and synthesize de novo cytokines and chemokines important in the amplification of the inflammatory response. One of the most prominent triggers of inflammatory responses is the cytokine TNF alpha. However, the intracellular signaling cascades triggered by TNF alpha are not fully understood. In this study we investigated the roles of SPHK on the TNF alpha-triggered responses on human primary monocytes. We show that TNFa rapidly triggers S1P generation and activation of SPHK. Moreover, our data shows that SPHK1 is the isoform activated by TNFa, and plays an essential role on the TNF alpha-triggered intracellular Ca2+ signals, degranulation, cytokine production, and activation of NF kappa B, thus suggesting a pivotal role for SPHK1 on the proinflammatory responses triggered by TNF alpha.