TNF-α Autocrine Feedback Loops in Human Monocytes: The Pro- and Anti-Inflammatory Roles of the TNF-α Receptors Support the Concept of Selective TNFR1 Blockade In Vivo

摘要: Selective TNFR1 blockade in inflammatory diseases is emerging as a clinical strategy. We studied the roles of two TNF-α receptors, and TNFR2, human monocytes, principal producer central to many driven diseases. hypothesised that has pro- anti-inflammatory effects on occurring differentially via TNFR2. Monocytes were isolated from healthy subjects exposed LPS, plus/minus addition blocking antibodies or its receptors. Pro- cytokine production was quantified using real-time PCR ELISAs. Cell surface expression TNFR1/2 measured by flow cytometry. demonstrated monocytes vary patterns Autocrine binding led sustained upregulation proinflammatory cytokines TNFR1. In contrast, autocrine TNFR2 upregulated cytokine, IL-10, without effect. responsible for soluble secreted clearing pericellular environment. did not change cell leaving this receptor free upregulate IL-10. These novel results support concept selective vivo order positive can be retained ligation.