Interleukin 11 signaling in 3T3-L1 adipocytes

Interleukin 11 (IL-11) is an anti-inflammatory cytokine with receptors located on most cell types and tissues throughout the body. Its anti-inflammatory properties are mediated through suppression of cytokine synthesis, in large part by prevention of NF-kappaB activation. As adipose tissue synthesizes and secretes cytokines involved in establishing insulin resistance and due to the ability of IL-11 to suppress cytokine synthesis, we initiated an investigation to determine the signal transduction pathways initiated by IL-11 in adipose tissue. Using the 3T3-L1 adipocyte cell culture model we demonstrate the rapid activation of the p44/42MAP kinase, PI3-kinase, and STATs 1 and 3. Activation of MAP kinase is demonstrated to lead to the downstream activation of p90 RSK (ribosomal S6 kinase) as well as ATF-1 and CREB. PI3-kinase appears to activate the downstream target of p70 S6 kinase resulting in phosphorylation of ribosomal protein S6. STAT phosphorylation appears to be initiated through PI3-kinase and to a lesser degree through p44/42 MAP kinase. These studies demonstrate the activation of three major signaling pathways and support a role for IL-11 in the regulation of both transcription and protein synthesis in fully differentiated adipocytes.