Physiological genomics
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Physiological genomics · Apr 2005
Expression of Eph receptors and their ligands, ephrins, during lipopolysaccharide fever in rats.
Erythropoietin-producing hepatocellular (Eph) receptor tyrosine kinases and their ligands, ephrins, are involved in embryogenesis and oncogenesis by mediating cell adhesion and migration. Although ephrins can be induced by bacterial LPS in vitro, whether they are involved in inflammation in vivo is unknown. Using differential mRNA display, we found that a febrigenic dose of LPS (50 microg/kg iv) induces a strong transcriptional upregulation of ephrin-A1 in rat liver. ⋯ Characteristic, counter-directed changes in expressional regulation of Eph receptors and their corresponding ligands were found: upregulation of EphA2, downregulation of ephrin-A1 in the liver and lung at phase 2; downregulation of EphB3, upregulation of ephrin-B2 in the liver at phase 2; downregulation of EphA1 and EphA3, upregulation of ephrins-A1 and -A3 in liver at phase 3. In the liver, transcriptional changes of EphA2 and EphB3 at phase 2 were confirmed at protein level. These coordinated, phase-specific responses suggest that different sets of ephrins and Eph receptors may be involved in cellular events (such as disruption of tissue barriers and leukocyte transmigration) underlying different stages of systemic inflammatory response to LPS.