Cannabinoid agonist WIN55,212 in vitro inhibits interleukin-6 (IL-6) and monocyte chemo-attractant protein-1 (MCP-1) release by rat pancreatic acini and in vivo induces dual effects on the course of acute pancreatitis

Petrella, Carla; Agostini, Simona; Alemà, G; Casolini, Paola; Carpino, F; Giuli, C.; Improta, Giovanna; Linari, G; Petrozza, Vincenzo; Broccardo, Maria

doi:10.1111/j.1365-2982.2010.01569.x

Cited by 19 publications

(20 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This effect could be completely abolished by previous administration of AM630, which furthermore shows that effects of JWH133 are mediated by CB 2 . In line with our findings, also in Michalski et al (42,43) as well as in Petrella et al (46) studies, decreased effects of the used nonselective cannabinoid agonists were reported after antagonization by AM630. Our finding that some parameters in the AM630-and JWH133-pretreated animals were elevated compared with nonpretreated pancreatitis animals can be explained by additional blockade of eCB at CB 2 .…”

Section: Discussionsupporting

confidence: 81%

“…Furthermore, cannabinoid receptors have been shown to play a role in the modulation of secretion of pancreatic enzymes by acinar cells (38), an effect potentially involved in the early phase of acute pancreatitis. Recently, a study showed that another nonselective CB 1 /CB 2 agonist, WIN55,212, had inhibitory effects on synthesis and secretion of proinflammatory cytokines by rat acinar cells in vitro (46). Since this effect was antagonized by AM630, a role of CB 2 was suggested.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Activation of cannabinoid receptor 2 reduces inflammation in acute experimental pancreatitis via intra-acinar activation of p38 and MK2-dependent mechanisms

Michler

Storr

Krämer

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

. Activation of cannabinoid receptor 2 reduces inflammation in acute experimental pancreatitis via intra-acinar activation of p38 and MK2-dependent mechanisms. Am J Physiol Gastrointest Liver Physiol 304: G181-G192, 2013. First published November 8, 2012 doi:10.1152/ajpgi.00133.2012.-The endocannabinoid system has been shown to mediate beneficial effects on gastrointestinal inflammation via cannabinoid receptors 1 (CB 1) and 2 (CB2). These receptors have also been reported to activate the MAP kinases p38 and c-Jun NH 2-terminal kinase (JNK), which are involved in early acinar events leading to acute pancreatitis and induction of proinflammatory cytokines. Our aim was to examine the role of cannabinoid receptor activation in an experimental model of acute pancreatitis and the potential involvement of MAP kinases. Cerulein pancreatitis was induced in wild-type, CB 1Ϫ/Ϫ, and MK2Ϫ/Ϫ mice pretreated with selective cannabinoid receptor agonists or antagonists. Severity of pancreatitis was determined by serum amylase and IL-6 levels, intracellular activation of pancreatic trypsinogen, lung myeloperoxidase activity, pancreatic edema, and histological examinations. Pancreatic lysates were investigated by Western blotting using phospho-specific antibodies against p38 and JNK. Quantitative PCR data, Western blotting experiments, and immunohistochemistry clearly show that CB 1 and CB2 are expressed in mouse pancreatic acini. During acute pancreatitis, an upregulation especially of CB 2 on apoptotic cells occurred. The unselective CB 1/CB2 agonist HU210 ameliorated pancreatitis in wild-type and CB 1Ϫ/Ϫ mice, indicating that this effect is mediated by CB 2. Furthermore, blockade of CB2, not CB1, with selective antagonists engraved pathology. Stimulation with a selective CB 2 agonist attenuated acute pancreatitis and an increased activation of p38 was observed in the acini. With use of MK2Ϫ/Ϫ mice, it could be demonstrated that this attenuation is dependent on MK2. Hence, using the MK2Ϫ/Ϫ mouse model we reveal a novel CB 2-activated and MAP kinase-dependent pathway that modulates cytokine expression and reduces pancreatic injury and affiliated complications. cannabinoids; CB 2; p38; MK2; experimental pancreatitis ACUTE PANCREATITIS HAS BEEN the subject of investigations for many years, and cytokines have become a new focus in the investigation of the pathophysiology of pancreatitis. Although the exact underlying mechanisms only begin to emerge, cytokines play a crucial role in the process of pancreatitis. Since multiple organ dysfunction syndrome is the primary cause for morbidity and mortality in acute pancreatitis (6, 64), there is a great need to understand the pathophysiological processes leading to this fatal complication. Here, TNF-␣ and IL-6 as proinflammatory cytokines play a predominant role (5, 6, 23). As a consequence of an inflammatory cascade triggered by induction of proinflammatory cytokines in acinar cells (39,45), neutrophil granulocytes immigrate into lung tissue (5, 49). This constitutes a key event in gene...

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Activation of cannabinoid receptor 2 reduces inflammation in acute experimental pancreatitis via intra-acinar activation of p38 and MK2-dependent mechanisms

Michler

Storr

Krämer

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…13Y17 It was shown that preadministered HU210, a synthetic specific CB1 agonist, protects against cerulein-induced mouse pancreatitis; otherwise, CB1 antagonist rimonabant attenuated the severity of AP in obese mice. 14,15 One of the endogenous cannabinoids, anandamide, when administered before the induction of AP, aggravated pancreatic damage and administered after the induction of AP, reduced the severity of AP, according to the experimental results of Dembinski et al 16 ; whereas Petrella et al 17 got the contrary results in which pretreatment with anandamide before the induction of AP worsened the inflammation, but posttreatment improved the course of the disease.…”

mentioning

confidence: 99%

Anti-Inflammatory Role of Cannabidiol and O-1602 in Cerulein-Induced Acute Pancreatitis in Mice

Feng²,

Li³

et al. 2013

Pancreas

View full text Add to dashboard Cite

Objectives: The anti-inflammatory effects of O-1602 and cannabidiol (CBD), the ligands of G proteinYcoupled receptor 55 (GPR55), on experimental acute pancreatitis (AP) were investigated.Methods: Acute pancreatitis was induced in C57BL mice by intraperitoneal injection of 50 Kg/kg cerulein hourly, with a total of 6 times. Drugs (O-1602, 10 mg/kg, or CBD, 0.5 mg/kg) were given by intraperitoneal injection 2 times at 30 minutes before the first injection and immediately before the fifth cerulein injection. At 3 hours after the last injection, the blood, the lungs, and the pancreas were harvested for the pancreatic enzyme activity, myeloperoxidase activity, and pro-inflammatory cytokines measurement; and the expressions of GPR55 mRNA and protein in the pancreas were detected.Results: Cannabidiol or O-1602 treatment significantly improved the pathological changes of mice with AP and decreased the enzyme activities, IL-6 and tumor necrosis factor > levels, and the myeloperoxidase activities in plasma and in the organ tissues. G proteinYcoupled receptor 55 mRNA and protein expressed in the pancreatic tissue, and the expressions were decreased in the mice with AP, and either CBD or O-1602 attenuated these changes to a certain extent.Conclusion: Cannabidiol and O-1602 showed anti-inflammatory effects in mice with AP and improved the expression of GPR55 in the pancreatic tissue as well.

show abstract

“…There are two G proteincoupled cannabinoid receptors in the human body, CB1 and CB2 receptors. CB1 receptor is mainly present in the central and peripheral nervous system and CB2 receptor is mainly present in immune cells and the GI tract (23). Both CB1 and CB2 receptors are weakly expressed in the normal pancreas, but this expression increases in the setting of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Severity and outcomes of acute alcoholic pancreatitis in cannabis users

Goyal

Guerreso

Smith

et al. 2017

Transl. Gastroenterol. Hepatol.

View full text Add to dashboard Cite

Cannabinoid agonist WIN55,212 in vitro inhibits interleukin-6 (IL-6) and monocyte chemo-attractant protein-1 (MCP-1) release by rat pancreatic acini and in vivo induces dual effects on the course of acute pancreatitis

Cited by 19 publications

References 63 publications

Activation of cannabinoid receptor 2 reduces inflammation in acute experimental pancreatitis via intra-acinar activation of p38 and MK2-dependent mechanisms

Activation of cannabinoid receptor 2 reduces inflammation in acute experimental pancreatitis via intra-acinar activation of p38 and MK2-dependent mechanisms

Anti-Inflammatory Role of Cannabidiol and O-1602 in Cerulein-Induced Acute Pancreatitis in Mice

Severity and outcomes of acute alcoholic pancreatitis in cannabis users

Contact Info

Product

Resources

About