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Pancreatic enzymes: Parallel between antigen digestion and enterocyte maturation

Hamid, Bashar (2011) MOBN13 20111
Degree Projects in Molecular Biology
Abstract
Abstract

Objective: The small intestinal epithelium is a highly complex system continuously renewed by a process involving cell proliferation and differentiation. In mammals, the physiological function of intestine is not fully mature at birth, and many factors could accelerate gut maturation. In the current study we hypothesized that the pancreatic enzymes could be one of such factors. In the same time we postulated the inflammation cascades and/or immune cell expan-
ion in the intestinal mucosa could be involved in this processes.
Materials and Methods: This study involved 2 experiments. In a first experiment 3 enzyme preparations have used to study their effects on small intestine. It were procine pancreatic enzymes (Creon),... (More)
Abstract

Objective: The small intestinal epithelium is a highly complex system continuously renewed by a process involving cell proliferation and differentiation. In mammals, the physiological function of intestine is not fully mature at birth, and many factors could accelerate gut maturation. In the current study we hypothesized that the pancreatic enzymes could be one of such factors. In the same time we postulated the inflammation cascades and/or immune cell expan-
ion in the intestinal mucosa could be involved in this processes.
Materials and Methods: This study involved 2 experiments. In a first experiment 3 enzyme preparations have used to study their effects on small intestine. It were procine pancreatic enzymes (Creon), pancreatic-like enzymes of microbial origin, and a third one was non pancreatic-like enzymes of microbial origin (Rovabio), given in two doses by intragastric gavage to 14 days old suckling rats. In the second experiment, the link between inflammation cascades and intestinal maturation was studied by blocking the Cyclooxygenase (COX) pathway using Ibuprofen and Celecoxib, administered orally one hour prior to enzyme gavages. In both experiments there were particular emphases on morphological and functional changes of enterocytes as parameters. Moreover, here, response of immune system to each of pancreatic preparations was further studied, using specific antibody against CD25 and CD45 antigen.
Results: The results showed both the porcine pancreatic enzymes and pancreatic-like enzymes of microbial origin have increased the weight of small intestine, mucosal sucrase and maltase activity, and the ratio of adult phenotype of enterocyte along the villi with significant values. Also the responses of the immune system to each one was various. However, small single dose of anti-inflammatory drugs did not block maturation; instead they had very mild effect on enterocyte development.
Conclusion: The results demonstrate that pancreatic and pancreatic-like preparations were participating in the signaling pathways involved in the gut maturation. Furthermore this maturation could be T-cell independent as with Creon. On the other hand, the maturation was slightly inhibited with Celocoxib, suggesting that the COX pathway maybe involved in the “mechanism(s)” that induced maturation in this model, if it was closed in a systematic way.

Popular science summary:

Pancreatic Enzymes: Parallel between antigen digestion and enterocyte maturation

The function of the small intestine reflects its three main roles: digestion, absorption of nutrients, and maintenance of a barrier against the external environment. The small intestinal lined by a single layer of epithelial cell which is a highly complex cells, continuously exposed to antigen (Ag) and continuously renewed by a process involving cell proliferation and differentiation. In mammals, physiological functions of this layer are not fully matured after birth, but within time and in response to many factors this layer matures. However, in some cases the complete maturation may be delayed for unknown reasons, allowing for the transfer of many Ag from lumen to the underlining layers, resulting in specific immune responses (unwanted reactions which could lead to organs damage). It was hypothesized that there are many factors could play important role in this process; acceleration or development of gut maturation. But at present the complete picture as to which types of materials could induce acceleration and why remains unknown.

In the current study we hypothesized that the pancreatic enzymes (mixture of lipase, protease and amylase; enzymes are always used to break down fat, protein, and starch respectively) could be one of such factors. To explore this hypothesis, we chose different materials; pancreatic enzymes and non pancreatic enzymes (control), and then studied their effect on the development of intestinal epithelial cells (IEC) of suckling rats. The results showed that only pancreatic materials have induced gut maturation with significant values compared with control groups, indicates the role of the pancreas in this process.

Nowadays, investigation of gut development is quite a challenge and attractive objective for many researchers in the gastrointestinal field. This attraction is based on the ample evidence between intestinal diseases and immature intestine which can solve by pancreatic enzymes for instance. Moreover the precocious maturation of intestine in the current study could give positive effect on the integrity of the other organs in mammals, especially during suckling period. The fact that the physiological functions of intestine is not fully mature at birth, (i.e. the maturation of gut is one of the most critical factors for survival and further development of the other organs). Taken together, pancreatic enzymes may offer therapeutic potential strategies for some diseases in future, opening a door for a new generation of therapies especially for treatment of immature intestine.




Advisor: Olena Prykhod’ko & Björn Weström
Master´s Degree Project in Immunology project 45 credit with specialization in medical biology
Department of biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Hamid, Bashar
supervisor
organization
course
MOBN13 20111
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
2206497
date added to LUP
2011-12-15 12:37:44
date last changed
2013-03-26 14:41:42
@misc{2206497,
  abstract     = {Abstract

Objective: The small intestinal epithelium is a highly complex system continuously renewed by a process involving cell proliferation and differentiation. In mammals, the physiological function of intestine is not fully mature at birth, and many factors could accelerate gut maturation. In the current study we hypothesized that the pancreatic enzymes could be one of such factors. In the same time we postulated the inflammation cascades and/or immune cell expan-
ion in the intestinal mucosa could be involved in this processes.
Materials and Methods: This study involved 2 experiments. In a first experiment 3 enzyme preparations have used to study their effects on small intestine. It were procine pancreatic enzymes (Creon), pancreatic-like enzymes of microbial origin, and a third one was non pancreatic-like enzymes of microbial origin (Rovabio), given in two doses by intragastric gavage to 14 days old suckling rats. In the second experiment, the link between inflammation cascades and intestinal maturation was studied by blocking the Cyclooxygenase (COX) pathway using Ibuprofen and Celecoxib, administered orally one hour prior to enzyme gavages. In both experiments there were particular emphases on morphological and functional changes of enterocytes as parameters. Moreover, here, response of immune system to each of pancreatic preparations was further studied, using specific antibody against CD25 and CD45 antigen.
Results: The results showed both the porcine pancreatic enzymes and pancreatic-like enzymes of microbial origin have increased the weight of small intestine, mucosal sucrase and maltase activity, and the ratio of adult phenotype of enterocyte along the villi with significant values. Also the responses of the immune system to each one was various. However, small single dose of anti-inflammatory drugs did not block maturation; instead they had very mild effect on enterocyte development.
Conclusion: The results demonstrate that pancreatic and pancreatic-like preparations were participating in the signaling pathways involved in the gut maturation. Furthermore this maturation could be T-cell independent as with Creon. On the other hand, the maturation was slightly inhibited with Celocoxib, suggesting that the COX pathway maybe involved in the “mechanism(s)” that induced maturation in this model, if it was closed in a systematic way.

Popular science summary:

Pancreatic Enzymes: Parallel between antigen digestion and enterocyte maturation

The function of the small intestine reflects its three main roles: digestion, absorption of nutrients, and maintenance of a barrier against the external environment. The small intestinal lined by a single layer of epithelial cell which is a highly complex cells, continuously exposed to antigen (Ag) and continuously renewed by a process involving cell proliferation and differentiation. In mammals, physiological functions of this layer are not fully matured after birth, but within time and in response to many factors this layer matures. However, in some cases the complete maturation may be delayed for unknown reasons, allowing for the transfer of many Ag from lumen to the underlining layers, resulting in specific immune responses (unwanted reactions which could lead to organs damage). It was hypothesized that there are many factors could play important role in this process; acceleration or development of gut maturation. But at present the complete picture as to which types of materials could induce acceleration and why remains unknown. 

In the current study we hypothesized that the pancreatic enzymes (mixture of lipase, protease and amylase; enzymes are always used to break down fat, protein, and starch respectively) could be one of such factors. To explore this hypothesis, we chose different materials; pancreatic enzymes and non pancreatic enzymes (control), and then studied their effect on the development of intestinal epithelial cells (IEC) of suckling rats. The results showed that only pancreatic materials have induced gut maturation with significant values compared with control groups, indicates the role of the pancreas in this process. 

Nowadays, investigation of gut development is quite a challenge and attractive objective for many researchers in the gastrointestinal field. This attraction is based on the ample evidence between intestinal diseases and immature intestine which can solve by pancreatic enzymes for instance. Moreover the precocious maturation of intestine in the current study could give positive effect on the integrity of the other organs in mammals, especially during suckling period. The fact that the physiological functions of intestine is not fully mature at birth, (i.e. the maturation of gut is one of the most critical factors for survival and further development of the other organs). Taken together, pancreatic enzymes may offer therapeutic potential strategies for some diseases in future, opening a door for a new generation of therapies especially for treatment of immature intestine.




Advisor: Olena Prykhod’ko & Björn Weström
Master´s Degree Project in Immunology project 45 credit with specialization in medical biology
Department of biology, Lund University},
  author       = {Hamid, Bashar},
  language     = {eng},
  note         = {Student Paper},
  title        = {Pancreatic enzymes: Parallel between antigen digestion and enterocyte maturation},
  year         = {2011},
}