Fig. 2.

Molecular profiles of classical IL-6 vs. trans-signaling. A. Classical IL-6 signaling leads to activation of the JAK/STAT, AKT and MAPK pathways to alter transcription. Release of cytokines leads to feedback inhibition through SOCS. B. Trans-signaling creates a shift towards greater JAK/STAT signaling than MAPK through suppression of SOCS and alterations in NFkB. This lack of feedback in concert with the increase in activation of JAK/STAT lead to greater transcription of cytokines and a pro-inflammatory state.