Role of cytokines and their inhibitors in acute pancreatitis.

Kingsnorth, Andrew

doi:10.1136/gut.40.1.1

Cited by 153 publications

(92 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The cause of death in most of these patients seems to be related to the pancreatic inflammation itself or even to infection associated with pancreatic necrosis (1). Severe cases are often the result of multiple organ failure, similar to that occurring in patients with septic shock (1,2). In these cases, proinflammatory cytokines (TNF-␣, IL-1␤, and IL-6) may play a central role and mediate the systemic complications of the disease (1,2).…”

Section: Il-6 Secretion By Human Pancreatic Periacinar Myofibroblastsmentioning

confidence: 99%

IL-6 Secretion by Human Pancreatic Periacinar Myofibroblasts in Response to Inflammatory Mediators

Shimada

Andoh

Hata

et al. 2002

The Journal of Immunology

131

116

View full text Add to dashboard Cite

There is increasing evidence that IL-6 plays an important role in the pathophysiology of acute pancreatitis via its broad proinflammatory actions. To identify the local biosynthetic site for IL-6 in human pancreas, we investigated IL-6 secretion in human pancreatic periacinar myofibroblasts. IL-6 secretion was determined by ELISA and Northern blotting. The activation of NF-κB was assessed by EMSA. The activation of mitogen-activated protein kinase (MAPK) was assessed by immunoblotting. IL-6 secretion was rapidly induced by IL-17, IL-1β, and TNF-α. EMSAs demonstrated that IL-17, IL-1β, and TNF-α induced NF-κB activation within 1.5 h after stimulation, and a blockade of NF-κB activation by the pyrrolidine derivative of dithiocarbamate and tosyl-phe-chloromethylketone markedly reduced the IL-17-, IL-1β-, or TNF-α-induced IL-6 gene expression. Furthermore, IL-17, IL-1β, and TNF-α induced a rapid activation of extracellular signal-related kinase p42/44 and p38 MAPKs, and specific MAPK inhibitors (SB203580, PD98059, and U0216) significantly reduced IL-17-, IL-1β-, or TNF-α-induced IL-6 secretion, indicating the role of MAPKs in the induction of IL-6. The combination of either IL-17 plus IL-1β or IL-17 plus TNF-α enhanced IL-6 secretion and IL-6 mRNA expression; in particular, the effects of IL-17 plus TNF-α were much stronger than those induced by IL-17 plus IL-1β. TNF-α-induced IL-6 mRNA degraded rapidly at any concentrations, and the combination of IL-17 and TNF-α markedly enhanced IL-6 mRNA stability. This indicates that the effects of IL-17 plus TNF-α were regulated at the post-transcriptional level. In conclusion, pancreatic periacinar myofibroblasts secreted a large amount of IL-6 in response to proinflammatory cytokines. These cells might play an important role in the pathogenesis of acute pancreatitis via IL-6 secretion.

show abstract

Section: Il-6 Secretion By Human Pancreatic Periacinar Myofibroblastsmentioning

confidence: 99%

IL-6 Secretion by Human Pancreatic Periacinar Myofibroblasts in Response to Inflammatory Mediators

Shimada

Andoh

Hata

et al. 2002

The Journal of Immunology

131

116

View full text Add to dashboard Cite

show abstract

“…It is a key regulator of other proinflammatory cytokines and of leukocyte adhesion molecules and it is a priming activator of immune cells (16). In recent years, several studies suggested that TNF alpha plays a pivotal role in the pathogenesis of acute pancreatitis.…”

Section: Discussionmentioning

confidence: 99%

Serum TNF-Alpha Levels in Acute and Chronic Pancreatitis

et al. 2009

View full text Add to dashboard Cite

AimResults: TNF-alpha concentrations were 13. 30±4.42 (7.04-21.35) pg/ml and 9.88±4.68 (3.99-27.73) pg/ml 10.09±1.01 (8.69-14.96) pg/ml in patients with acute and chronic pancreatitis and healthy controls respectively. TNF-alpha concentrations were significantly higher in patients with acute pancreatitis than the patients with chronic pancreatitis. But there was no significant difference between healthy controls and patients with either acute or chronic pancreatitis for TNF-alpha levels. There was no significant correlation between TNF-alpha concentrations and pancreatic enzyme levels. Conclusion:We concluded that in acute pancreatitis TNF-alpha levels were higher than the chronic form of the disease. But its concentrations did not correlate with the severity of the disease. By investigation of the other inflammatory markers and acute phase reactants with TNF-alpha, this process will be more clarified.

show abstract

“…In AP, cytokines and chemokines produced both locally within the pancreas and remotely (by macrophages in the peritoneum) provoke inflammatory responses through autacrine and paracrine regulatory mechanisms [10]. Several factors including tumor necrosis factor (TNF)-, IL-1, IL-8 control the severity of AP, and are correlated with clinical outcomes [6,9,11,12]. Some recent reports show an improved survival and attenuation of local and remote inflammatory changes in experimental models of AP following cytokine blockade [13,14].…”

Section: Introductionmentioning

confidence: 99%

“…Leukocytes adhere to endothelial cells during inflammation after exposure to a variety of chemical mediators and inflammatory cytokines released at sites of tissue damage. These *Address correspondence to this author at the Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA; Tel: 318-675-4151; Fax: 503-907-7543; E-mail: jalexa@lsuhsc.edu trigger the synthesis, mobilization and presentation of endothelial adhesion molecules [6]. In pancreatitis, the adhesion molecule ICAM-1 and chemokines, such as macrophage inflammatory peptide 1-(MIP1-) and interleukin-8 (IL-8), are implicated in the neutrophil sequestration which occurs in the pancreas and the lungs in AP, and appear to be important initial events in triggering AP [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

TNF-α Regulated MAdCAM-1 Expression in Pancreatic Microvessel Endothelium: A Possible Role for MAdCAM-1 in Pancreatitis?

Ando¹,

Jordan²,

Wang³

et al. 2008

TOGASJ

View full text Add to dashboard Cite

Abstract:The Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) is associated with active inflammatory bowel disease; however MAdCAM-1 expression in the pancreas has not been previously documented. This study investigated MAdCAM-1 expression during cerulein-induced pancreatitis, and examined MAdCAM-1 expression, regulation and function in cytokine-treated pancreatic endothelial cells. Acute pancreatitis was induced by serial injections of cerulein over 10h, at which point tissue samples were collected. Pancreas endothelial cells (PMEC) were prepared from H2Kb-tsA58 (Immortomouse) mice. MAdCAM-1 expression was examined by immunoblotting after cytokine (TNF-, ILor IFN-) stimulation. 2 nd messages regulating MAdCAM-1 were studied by adding pharmacological blockers prior to cytokines. MAdCAM-1 dependent lymphocyte adhesion was monitored using 4 7-integrin expressing lymphocytes. In cerulein-pancreatitis, MAdCAM-1 was upregulated by 10h, and closely correlated with histopathology. In PMEC, only TNF-induced MAdCAM-1 dose (0-20ng/ml) and time (>12h-48h) dependently. MAdCAM-1 expression was PKC, tyrosine kinase, p38 MAPK, and NF-B-PARP dependent. PMEC-lymphocyte adhesion was increased by TNF-, and significantly reduced by MAdCAM-1 antibody. MAdCAM-1 is induced in the inflamed pancreas, and in TNF-stimulated PMEC, and may represent a novel determinant of pancreatic-lymphocyte recruitment in inflammation. PMEC cells might provide a useful system to study mechanisms related to both acute and chronic pancreatitis.

show abstract

Role of cytokines and their inhibitors in acute pancreatitis.

Cited by 153 publications

References 54 publications

IL-6 Secretion by Human Pancreatic Periacinar Myofibroblasts in Response to Inflammatory Mediators

IL-6 Secretion by Human Pancreatic Periacinar Myofibroblasts in Response to Inflammatory Mediators

Serum TNF-Alpha Levels in Acute and Chronic Pancreatitis

TNF-α Regulated MAdCAM-1 Expression in Pancreatic Microvessel Endothelium: A Possible Role for MAdCAM-1 in Pancreatitis?

Contact Info

Product

Resources

About