MCPIP1 alleviated alcohol-induced immune dysfunction via the MAPK/ERK signaling pathway.

RATIONALE: In recent years, monocyte chemotactic protein-induced protein 1 (MCPIP1) has been reported to control inflammation via IL-10.

OBJECTIVES

The aims of this study were to determine (1) whether MCPIP1 can repair damage to the immune system after alcohol use and (2) whether MCPIP1 can repair the immune function impaired by alcohol use through the MAPK/ERK signaling pathway. Our results will inform the treatment of immune dysfunction caused by alcohol consumption.

METHODS

Scrambled shRNA or MCPIP-1-shRNA carried by the lentiviral vector (50μl each at 1×108TU/ml) was injected retrogradely through the pancreatic duct to pretreat male C57BL/6 mice. Five days after the injection, mice were exposed to intragastric ethanol infusion (5g/kg, 25% ethanol w/v) daily or vehicle for 10 days.

RESULTS

MCPIP-1 protein was increased in the pancreas after alcohol exposure. MCPIP-1 shRNA specifically decreased MCPIP-1 protein expression and mRNA level in the pancreas. Specific knockdown of MCPIP-1 exacerbates pancreatic necrosis, interstitial edema, and inflammatory infiltrates after alcohol exposure. Meanwhile, specific knockdown of MCPIP-1 also increased pancreatic pro-inflammatory cytokine (IL-6 and IL-1β), chemokine MCP-1, and chemokine receptor 2 (CCR2) after alcohol exposure. What's more, p-JNK and p-ERK in the pancreas were all similarly increased in response to pancreas-specific knockdown of MCPIP-1 during alcohol exposure.

CONCLUSIONS

Taken together, the results above suggested that MCPIP1 repairs the immune function impaired by alcohol use via stimulating JNK and ERK pathways. Our results will inform the treatment of immune dysfunction caused by alcohol consumption.