Yanjie Shen1, Kai Zhang2,3, Rui Wang1, Shuaichen Sun1, Yating Yang2,3, Yitan Yao2,3, Huanzhong Liu4,5, Zhenhua Ren6. 1. Department of Anatomy, Anhui Medical University, Hefei, 230032, China. 2. Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China. 3. Anhui Mental Health Center, Anhui Medical University, Hefei, China. 4. Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China. huanzhongliu@ahmu.edu.cn. 5. Anhui Mental Health Center, Anhui Medical University, Hefei, China. huanzhongliu@ahmu.edu.cn. 6. Department of Anatomy, Anhui Medical University, Hefei, 230032, China. renzhenhua@ahmu.edu.cn.
Abstract
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.
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.
Authors: Shin-Heng Chiou; Ian P Winters; Jing Wang; Santiago Naranjo; Crissy Dudgeon; Fiona B Tamburini; Jennifer J Brady; Dian Yang; Barbara M Grüner; Chen-Hua Chuang; Deborah R Caswell; Hong Zeng; Pauline Chu; Grace E Kim; Darren R Carpizo; Seung K Kim; Monte M Winslow Journal: Genes Dev Date: 2015-07-15 Impact factor: 11.361