Selective inhibition of IL-6 trans-signaling by a miniaturized, optimized chimeric soluble gp130 inhibits T17 cell expansion.

The cytokine interleukin-6 (IL-6) signals through three mechanisms called classic signaling, trans-signaling, and trans-presentation. IL-6 trans-signaling is distinctly mediated through a soluble form of its transmembrane receptor IL-6R (sIL-6R) and the coreceptor gp130 and is implicated in multiple autoimmune diseases. Although a soluble form of gp130 (sgp130) inhibits only IL-6 trans-signaling, it also blocks an analogous trans-signaling mechanism of IL-11 and its soluble receptor sIL-11R.

Binding and intracellular transport of 25-hydroxycholesterol by Niemann-Pick C2 protein.

Side-chain oxidized cholesterol derivatives, like 25-hydroxycholesterol (25-OH-Chol) are important regulators of cellular cholesterol homeostasis. How transport of oxysterols through the endo-lysosomal pathway contributes to their biological function is not clear. The Niemann-Pick C2 protein (NPC2) is a small lysosomal sterol transfer protein required for export of cholesterol from late endosomes and lysosomes (LE/LYSs).

Soluble gp130 prevents interleukin-6 and interleukin-11 cluster signaling but not intracellular autocrine responses.

Interleukin-6 (IL-6) is a proinflammatory cytokine of the IL-6 family, members of which signal through a complex of a cytokine-specific receptor and the signal-transducing subunit gp130. The interaction of IL-6 with the membrane-bound IL-6 receptor (IL-6R) and gp130 stimulates "classic signaling," whereas the binding of IL-6 and a soluble version of the IL-6R to gp130 stimulates "trans-signaling." Alternatively, "cluster signaling" occurs when membrane-bound IL-6:IL-6R complexes on transmitter cells activate gp130 receptors on neighboring receiver cells.

The balance of interleukin (IL)-6, IL-6·soluble IL-6 receptor (sIL-6R), and IL-6·sIL-6R·sgp130 complexes allows simultaneous classic and trans-signaling.

Interleukin (IL-)6 is the major pro-inflammatory cytokine within the IL-6 family. IL-6 signals via glycoprotein 130 (gp130) and the membrane-bound or soluble IL-6 receptor (IL-6R), referred to as classic or trans-signaling, respectively. Whereas inflammation triggers IL-6 expression, eventually rising to nanogram/ml serum levels, soluble IL-6R (sIL-6R) and soluble gp130 (sgp130) are constitutively present in the upper nanogram/ml range.