Fig. 8: Proposed mechanism of action of ROCK1 inhibition.
From: ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease
Acute GVHD pathophysiology (left panel) involves expansion of MPO positive neutrophils and upregulation of ROCK1 expression in myeloid cells. ROCK1/2-inhibition in mice leads to reduced IL-6 and TNF levels, thereby reducing aGVHD histopathology and improving survival. ROCK1/2-inhibition counteracts multiple pathogenic events in dendritic cells (blue panel) and macrophages (green panel) including TNF production by DCs and macrophages, antigen presentation and migration. Moreover, ROCK1/2-inhibition in macrophages or dendritic cells prior to transfer reduces aGVHD severity. On the signaling level ROCK1/2-inhibition interferes with the NF-κB pathway activity.
