CD137 ligand trigger in phospholipid signalling cascade in a monocyte cell line

Abstract

CD137 and CD137L are members of TNF receptor and TNF superfamily, respectively, in which bidirectional signalling has been shown. CD137L is constitutively expressed by monocytes. Monocytes migrate to inflammation site to support immune response. Sphingolipid metabolites have emerged as important second messengers, mediating signalling pathways triggered in immune cells including monocytes. Sphingosine kinase (SphK) is implicated in inflammation, autoimmune diseases, allergies and cancer development. Here, we show that reverse signalling by CD137L is mediated by SphK. SphK activity is shown to reach its peak activity at 10 minutes upon activation of CD137L. The SphK inhibitors, DMS and compound 5c, inhibited the secretion of inflammatory chemokine IL-8, MCP-1, MIP-1alpha and MIP-1beta; in which some are important in leukocytes homing. The release of these chemokines was also reduced by DMS and 5c. This study shows that SphK plays a role in the signal transduction induced by CD137L.