Changes in the expression of LIMP-2 during cerulein-induced pancreatitis in rats: Effect of inhibition of leukocyte infiltration,cAMP and MAPKs early on in its development |
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| Affiliation: | 1. Department of Biochemistry and Molecular Biology, University of Salamanca, IBSAL (Instituto de Investigación Biomédica de Salamanca), Spain;2. Institute of Neurosciences of Castilla y León (INCYL), University of Salamanca, Spain;3. Department of Physiology and Pharmacology, University of Salamanca, IBSAL (Instituto de Investigación Biomédica de Salamanca), Spain;1. Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;2. Department of Surgery, the Third Affiliated Hospital of Jianghan University, 259 Baixiu Street, Wuhan 430030, China;1. Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, China;2. Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Institute of Basic Medical Sciences and School of Basic Medicine, Beijing 100005, China;3. Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China;1. Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Level 6, Herschel Building, Brewery Lane, Newcastle upon Tyne NE1 7RU, UK;1. Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania;2. Gastroenterology Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;3. Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;4. Center for Endoscopic Innovation, Research and Training, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania |
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| Abstract: | Lysosomal integral membrane protein-2 (LIMP-2) is an important protein in lysosomal biogenesis and function and also plays a role in the tissue inflammatory response. It is known that lysosomes play a central role in acute pancreatitis, with inflammatory cell infiltration triggering the disease early on. In this study we report increases in pancreatic LIMP-2 protein and mRNA levels as early events that occur during the development of cerulein (Cer)-induced acute pancreatitis (AP) in rats. GdCl3, a macrophage inhibitor, but not FK506, a T lymphocyte inhibitor, was able to reverse the increase in LIMP-2 expression after Cer treatment, although such reversion was abolished if the animals were depleted of neutrophils due to a vinblastine sulfate pre-treatment. Immunostaining revealed that the cellular source of LIMP-2 was mainly acinar cells. Additionally, pre-treatments with the MAPKs inhibitors SP600125 and PD98059, inhibitors of JNK and ERK½ activation, respectively, but not of rolipram, a type IV phosphodiesterase inhibitor, suppressed the increase in the expression of LIMP-2 after Cer administration. Together, these results indicate that neutrophils are able to drive a macrophage activation that would regulate the increase in LIMP-2 expression during the early phase of Cer-induced AP, with the stress kinases JNK and ERK½ also playing a coordinated role in the increase of LIMP-2 expression due to Cer. |
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| Keywords: | LIMP-2 Infiltration inhibition MAPK inhibition Cerulein Experimental acute pancreatitis |
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