Gastrointestinal inflammation prevented by protein sorting factor found in cells lining the gut
Figure 1: AP-1B expression in gut epithelial cells prevents bacteria from entering the gut and causing inflammatory bowel diseases. © 2011 Koji Hase
The gastrointestinal tract is lined with intestinal epithelial cells (IECs) that maintain gut health by keeping bacteria and pro-inflammatory immune cells from infiltrating gut tissues. Now, a team of researchers in Japan has shown that a protein in these cells, which is responsible for sorting many proteins to particular portions of the IEC surface, plays a key role in IEC modulation of gut inflammation.
IECs are polarized cells, with a bottom surface that attaches to deeper gut tissues, and a top surface that faces the inside of the gut, where it is exposed to ingested food and gut-resident bacteria. Proteins that are created in the cell are sorted preferentially to either the top or the bottom portion of the IEC. For example, cytokine receptors are shuttled mainly to the bottom of IECs so they can respond to cytokines released by immune cells within deeper gut tissues. Led by Koji Hase at the RIKEN Research Center for Allergy and Immunology in Yokohama, the researchers thought that disruption of proper protein sorting could affect the ability of IECs to properly respond to their environment.
To test their theory, the researchers generated mice lacking the μ1B subunit for a sorting protein called adaptor protein-1B (AP-1B). These mice developed an inflammatory gut disease called colitis, in which large number of immune cells infiltrated the gut. Mice lacking AP-1B expressed fewer antibacterial proteins, allowing bacteria to attack gut tissue (Fig. 1). Hase and colleagues showed that this bacterial entry enhanced immune cell recruitment into the gut, because antibiotics could reduce the inflammation in these mice.
Cytokines such as interleukin-17 (IL-17) are responsible for inducing antibacterial protein expression in IECs. However, the researchers found that cells lacking AP-IB were unable to properly sort cytokine receptors, including the IL-17 receptor, to the appropriate portion of the IEC membrane. This suggested that IECs may have failed to properly respond to IL-17 because its receptors were in the wrong part of the cell.
When Hase and colleagues examined IECs in humans with an inflammatory bowel condition called Crohns disease, they found that expression of the μ1B subunit was reduced, and that one cytokine receptor seemed to sort to the wrong portion of the IEC surface. AP-1B-dependent protein sorting therefore seems to control epithelial immune functions that keep the human gut healthy, explains Hase. Enhancing the expression of μ1B could be a potential therapy for Crohn's disease, the team concludes.
More information: Takahashi, D., Hase, K., Kimura, S., Nakatsu, F., Ohmae, M., Mandai, Y., Sato, T., Date, Y., Ebisawa, M., Kato, T., et al. The epithelia-specific membrane trafficking factor AP-1B controls gut immune homeostasis in mice. Gastroenterology 141, 621632 (2011). www.gastrojournal.… 1-1/abstract
Provided by RIKEN
- Researchers find gut bacteria teaches immune cells to see them as friendly Sep 22, 2011 | not rated yet | 0
- Transcription factor regulates protein that dampens immune responses Jun 17, 2011 | not rated yet | 0
- Bacteria enter via mucus-making gut cells Oct 03, 2011 | not rated yet | 0
- Stress affects the balance of bacteria in the gut and immune response Mar 21, 2011 | not rated yet | 0
- Friend or Foe? Scientists Determine How the Intestine Keeps Us Safe From Microbial Invaders Feb 21, 2007 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be a term called "intestinal metaplasia" of stomach
10 hours ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
- More from Physics Forums - Medical Sciences
More news stories
Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement produced from beef, oysters, and soy. Proven to improve cognition and slow memory loss, it's a popular treatment for older ...
Medical research 4 hours ago | 5 / 5 (1) | 0 |
Researchers at Emory University have identified a protein that stimulates a pair of "orphan receptors" found in the brain, solving a long-standing biological puzzle and possibly leading to future treatments for neurological ...
Medical research 5 hours ago | not rated yet | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
Medical research 5 hours ago | 4.5 / 5 (2) | 0 |
Researchers at the University of Illinois at Chicago College of Medicine will study gender differences in how the heart uses and stores fat—its main energy source—and how changes in fat metabolism play ...
Medical research 8 hours ago | not rated yet | 0
Nearly 20 percent of kidneys that are recovered from deceased donors in the U.S. are refused for transplant due to factors ranging from scarring in small blood vessels of the kidney's filtering units to the organ going too ...
Medical research May 20, 2013 | 5 / 5 (2) | 0 |
A drug commonly used to treat depression and anxiety may improve a stress-related heart condition in people with stable coronary heart disease, according to researchers at Duke Medicine.
57 minutes ago | not rated yet | 0 |
(HealthDay)—The overall health of Americans isn't improving much, with about six in 10 people either overweight or obese and large numbers engaging in unhealthy behaviors like smoking, heavy drinking or ...
1 hour ago | not rated yet | 0
(HealthDay)—In 2008 to 2010, the prevalence of key health behaviors among U.S. adults varied, with about one in five adults current smokers and 62.1 percent overweight or obese, according to a report presented ...
57 minutes ago | not rated yet | 0
(HealthDay)—Factors such as increased case finding may explain why Michigan had half of the total spinal infections associated with contaminated methylprednisolone acetate in the recent fungal meningitis ...
47 minutes ago | not rated yet | 0
Early use of tracheostomy for mechanically ventilated patients not associated with improved survival
For critically ill patients receiving mechanical ventilation, early tracheostomy (within the first 4 days after admission) was not associated with an improvement in the risk of death within 30 days compared to patients who ...
57 minutes ago | not rated yet | 0
(HealthDay)—Three-quarters of public schools in the metro Atlanta area contain microbes, including bacteria indicating the presence of fecal matter, according to research published in the May 17 issue of ...
37 minutes ago | not rated yet | 0