Inhibition of PAK1 alleviates cerulein-induced acute pancreatitis via p38 and NF-κB pathways.

Acute pancreatitis is a life-threatening disease accompanied by systemic inflammatory response. NF-kB and p38 signal pathway are activated in acute pancreatitis induced by cerulein. And PAKs are multifunctional effectors of Rho GTPases with kinase activity. In this study, the function of PAK1 in acute pancreatitis was investigated, and found that PAK1 was up-regulated in pancreas of acute pancreatitis mice model, and led to NF-kB and p38 pathway activation. PAK1 inhibition by shRNA or small molecule inhibitor FRAX597 decreased NF-kB and p38 activity, also alleviated the pathological damage in the pancreas of acute pancreatitis mice model, including decreasing the amylase and lipase level in serum, decreasing the levels of tumor necrosis factor-α, interleukin -6 and interleukin-1β in acute pancreatitis. These results suggested that PAK1 inhibition protects against acute pancreatitis by inhibiting NF-κB and p38 pathways, and indicated that PAK1 is a potential therapy to alleviate acute pancreatitis patients in clinic, and these need to be explored further.