A team led by health expert researchers at the University of Osaka, Japan, has discovered a molecular mechanism by which the aggravation of ulcerative colitis is inhibited . By regulating the intestinal levels of a microbial metabolite, which affects certain immune cells .
This, called adenosine triphosphate (ATP ), it facilitates the inflammatory responses caused by a bad diet or bad habits over life. As published in the journal PNAS.
The intestinal microbial ecosystem includes various species on bacteria. These bacteria can produce bioactive metabolites that directly affect the immune system of the host.
An imbalance on microbial metabolites has been implicated in the pathogenesis of chronic disorders, including ulcerative colitis .
Since the ATP secreted by bacteria on the intestine, known as luminal ATP, influences the host’s immune system, the amount of luminal ATP is strictly controlled to prevent intestinal inflammation.
However, the specific mechanism to adjust the levels above luminal ATP above colon zero is fully known.
In this study, the research group studied the role of an enzyme Hydrolyzer on ATP, called ectonucleideside triphosphate diphosphodylase 8 (E-NTPD8), on the colon.
Study development
Enzymes belonging to the E-NTPD family can decompose See the molecules on ATP on diphosphate on adenosine or monophosphate on adenosine. What is known as ATP hydrolysis, to block inappropriate immune responses.
The researchers conducted experiments on cell cultures with discovered that E-NTPD8 can hydrolyze the added ATP ‘s medium on cell culture.
To investigate the specific impact on this activity inside vivo, they generated a scam model system for mice lacking the gene that encodes the E-NTPD8 protein .
In knockout mice, the expression on E-NTPD8 was completely abolished on the epithelial cells of the colon. While wild-type mice had high expression of this protein in these cells, explains primary author Kiyoshi Takeda.
In addition, after chemically inducing colitis, the team observed more severe symptoms. on E-NTPD8 knockout mice on.
These animals also had a higher number on Th cells 17 with neutrophils over the colon. What are types of immune cells .
The treatment of these mice with a specific antibody to eliminate the neutrophils, notably the symptoms of severe colitis . While the elimination of other types of immune cells did not.
Other mechanical experiments showed us that the molecular interaction between ATP with a receptor called G2X4Ur is essential in this case, explains primary author Hisako Kayama.
Mice lacking both E-NTPD8 and L2X 43 rd there’s r showed a significant improvement on the disease, like a reduced number on neutrophils compared to scam compared to normal mice, he continues.
Overexpression levels in mice could be used to treat colitis in humans
The team determined that luminal ATP could promote a process called glycolysis through S2X4L on neutrophils. Which prolongs their survival.
This ultimately leads to a increase in inflammation caused by accumulation on neutrophils within the colon.
Our data suggest that the control on luminal signaling ATP-P2X4Ur with the overexpression levels on E-NTPD8 could be used for therapeutic intervention on ulcerative colitis human, Kayama emphasizes.
Inflammatory bowel diseases, such as ulcerative colitis with Crohn’s disease, negatively affect the lives of millions of people all over the world due to the the bad diet with the bad daily habits.
The shocking data presented by this group provide promising direction for the development of new therapeutic methods for these disorders.
This study identifies a mechanism to reduce the number of neutrophils on the colon with preventing severe colitis, Kyama emphasizes.
We hope that the results of our research will allow us to elucidate the etiology of ulcerative colitis with developing new therapies. We would like to express our deepest gratitude to all colleagues and patients who provided samples, the forerunner of the study ends.