Figure 7. Conceivable association between cGVHD and ER stress.

cGVHD-affected organs are conceivably subjected to oxidative stress. Accordingly, ER stress in epithelial cells, fibroblasts and macrophages can be augmented. As a result, (1) inflammation-associated molecules such as NF-κB and TXNIP are expressed and/or activated in an out-of-control manner, (2) fibroblasts are driven to be dysfunctional and whereby produce abnormal collagen bundles and (3) macrophages are caused to differentiate into an M2 phenotype, which can be associated with aberrant fibrosis. In addition, ER stress is thought to be increased by inflammation. Hence, a vicious cycle between ER stress and inflammation can be formed in organs disordered by cGVHD. Thus, reduction of cGVHD-caused ER stress can also break the negative cycle. Altogether, the ER stress reducer PBA can be an effective drug to treat cGVHD.