Adipocytes play important roles in lipid storage, energy homeostasis and whole body insulin sensitivity. Studies in the last two decades have identified the hormones and cytokines that activate specific STATs in adipocytes in vitro and in vivo. Five of the seven STAT family members are expressed in adipocyte (STATs 1, 3, 5A, 5B and 6). Many transcription factors, including STATs, have been show...

This work focuses on the role of IL-6 in the hepatic acute phase response. A kinetic model of the signal transduction network in hepatocytes stimulated by IL-6 has been developed. Signaling induced by the IL-6 family of cytokines involves the activation of two major pathways: the JAK (Janus-associated kinases)/ STAT (signal transducers and transcription factors) and the MAPK (mitogen-activated ...

BACKGROUND Activation of the heart renin-angiotensin system (RAS) under pathophysiological conditions has been correlated with the development of ischemic injury. The binding of angiotensin II to its receptors triggers induction of several, perhaps multifunctional, intracellular signaling pathways, notable among them the Janus kinase/signal transducer and activator of transcription (JAK/STAT) p...

OX40 (CD134) is expressed on activated T cells; its ligand, OX40 ligand (OX40L) is expressed on dendritic cells, B cells, and activated endothelial cells. To determine how OX40-OX40L interaction affects graft-versus-host disease (GVHD), we used antagonistic anti-OX40L monoclonal antibody (mAb) or OX40(-/-) donor or OX40L(-/-) recipient mice. Similar degrees of GVHD reduction were observed with ...

Adrenomedullin (ADM), a secretory peptide with multiple functions in physiological to pathological conditions, is upregulated in several human cancers, including brain, breast, colon, prostate, and lung cancer. However, the molecular mechanisms underlying the regulation of ADM expression in cancerous cells are not fully understood. Here, we report that oncostatin M (OSM), a cytokine belonging t...

Interleukin-6 (IL-6) is one of the most important inflammatory cytokines. IL-6 is unique in signaling via a membrane bound and a soluble receptor. Intriguingly, these two pathways strongly differ in their biologic consequences. While classic IL-6 signaling via the membrane bound receptor is mainly regenerative and protective, IL-6 trans-signaling via the soluble IL-6R is rather pro-inflammatory...

The rat serine proteinase inhibitor 3 gene is activated by interleukin 6 (IL-6) and glucocorticoids in hepatic cells. We report here that a 147 bp promoter is sufficient for both IL-6 stimulation and glucocorticoid enhancement of IL-6 induced transcription. Within this region we identified two functional elements binding transcription factors from the C/EBP (CCAAT/enhancer binding proteins) and...

The development and resolution of an inflammatory process are regulated by a complex interplay among cytokines that have pro- and anti-inflammatory effects. Effective and sustained action of a proinflammatory cytokine depends on synergy with other inflammatory cytokines and antagonism of opposing cytokines that are often highly expressed at inflammatory sites. We analyzed the effects of the inf...