Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Cox-2 enzyme plays important role regulating acute pancreatitis and associated lung injury


New study identifies an enzyme associated with pancreatic inflammation

Bethesda, MD – Clinical acute pancreatitis can present with varying degrees of severity The chief causes of this disorder are gallstones, gallbladder-related disease and alcohol use. Viral infection, mumps, and certain medications such as corticosteroids, diuretics, and tetracycline are other causes. In adults, the disorder is frequently associated with lung injury, manifesting itself as adult respiratory distress syndrome.


While the catalyst for pancreatitis is not well known, it is thought that enzymes normally secreted by the pancreas in an inactive form become activated inside the pancreas and start to digest the pancreatic tissue. This process is called autodigestion and causes swelling, hemorrhage, and damage to the blood vessels. An attack may last for 48 hours, and damage to the Cyclooxygenase-2 (COX-2), a widely distributed enzyme, plays an important role in pancreatic inflammation.

The initiation of prostanoid synthesis from arachidonic acid involves the enzyme cyclooxygenase (COX), an enzyme that is also referred to as PGH synthase or PG endoperoxide synthase, because it is also the rate limiting enzyme for PGE2 synthesis.

Two COX isoforms have been identified; first, as a constitutive form (COX-1), which is thought to have an important housekeeping function; and second, as an inducible form (COX-2), which has been implicated as an important pro-inflammatory mediator. COX-2 is up-regulated in response to a variety of pro-inflammatory stimuli including IL-1, TNF, and bacterial lipopolysaccharide. COX-2 mRNA and protein levels are increased during experimental pancreatitis, but the role of COX-2 in pancreatitis has heretofore not been well defined.

The Study

A new study has explored the role of COX-2 in acute pancreatitis and pancreatitis-associated lung injury. The protocols entailed pretreating selected mice with COX-2 inhibitors, whereas other mice were bred with genetic deletion of COX-2. Pancreatitis was induced via supramaximal secretagogue stimulation.

The authors of "Inhibition Of Cyclooxygenase-2 Ameliorates the Severity Of Pancreatitis And Associated Lung Injury," are Albert M. Song, Lakshmi Bhagat, Vijay P. Singh, G. D. Van Acker, Michael L. Steer, and Ashok K. Saluja, all from the Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA. Their findings appear in the November, 2002 edition of the American Journal of Physiology – Gastrointestinal and Liver Physiology. The journal is one of 14 publications published each month by the American Physiological Society (APS).


Pancreatitis was induced in the mice with COX-2 inhibitors, and those bred with genetic deletion of COX-2 by 12 hourly injections of cerulein. The severity of pancreatitis was assessed by measuring serum amylase, pancreatic trypsin activity, intrapancreatic sequestration of neutrophils, and acinar cell necrosis. The severity of lung injury was evaluated by measuring lactate dehydrogenase levels in the bronchoalveolar lavage fluid and by quantitating neutrophil sequestration in the lung.

Two groups of studies were performed to evaluate the role of COX-2 in pancreatitis. The first involved use of genetically altered mice that do not express COX-2, whereas the second involved administration, to wild-type mice, of agents known to inhibit COX-2. Both groups of studies yielded similar results. Either genetic deletion or pharmacological inhibition of COX-2 resulted in a marked reduction in the severity of secretagogue-induced pancreatitis. Both approaches also resulted in a marked reduction in the severity of pancreatitis-associated lung injury.


The researchers found that:

· pancreatic COX-2 mRNA levels rose within 15 minutes of the start of cerulein administration and that pancreatic COX-2 protein levels were increased within four hours of cerulein administration; and
· these observations suggest that COX-2 might play an important role in regulating the severity of pancreatitis and, possibly, of pancreatitis-associated lung injury as well.

This reduction in pancreatitis and lung-injury severity, brought about by interfering with COX-2, led to a conclusion that COX-2 plays an important pro-inflammatory role in both pancreatitis and its associated lung injury.

The mechanisms by which COX-2 might promote inflammation in pancreatitis are not immediately obvious. The researchers considered the possibility that it might modulate the early intra-acinar cell events that characterize this model of pancreatitis. These include activation of trypsinogen and NF-ÊB, two temporally and mechanistically parallel events that occur within 30 min of the start of cerulein administration. The findings revealed that neither cerulein-induced trypsinogen activation nor cerulein-induced early NF-ÊB activation were altered by COX-2 deletion after 30 minutes of cerulein administration.


These studies indicate that COX-2 plays an important pro-inflammatory role in pancreatitis and pancreatitis-associated lung injury. COX-2 appears to regulate the severity of pancreatitis via mechanisms that are downstream to the early cell events. The pro-inflammatory effects of COX-2 in this model of pancreatitis may be multifactorial and involve, among other things, alterations in various enzyme expressions, specifically HSP70, iNOS, and neutrophil function.

Further studies will clearly be needed to identify those mechanisms, but regardless of the results of those studies, the observations reported in this study indicate that pharmacological interventions that inhibit COX-2 may prove beneficial in the prevention and/or treatment of acute pancreatitis.

Source: November 2002 edition of the American Journal of Physiology – Gastrointestinal and Liver Physiology.

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

Donna Krupa | EurekAlert!

More articles from Health and Medicine:

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Development and Fast Analysis of 3D Printed HF Components

19.03.2018 | Trade Fair News

In monogamous species, a compatible partner is more important than an ornamented one

19.03.2018 | Life Sciences

Signaling Pathways to the Nucleus

19.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>