InStem finds How to turn off Chronic Inflammatory Diseases
Insights into perinatal skin development directs how to turn of Chronic Inflammatory Diseases. A laboratory model for treatment of chronic inflammation has been established by research team from InStem – India
When the immune system goes rogue, the double edged sword of inflammation is turned against the very body it is supposed to protect. Long-lived immune reactions caused by damaged cells can lead to chronic inflammation and diseases such as osteoarthritis, rheumatoid arthritis and fibrosis. Now, a team of scientists from the Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, have gained new insights into how chronic inflammation can develop. Furthermore, the team have designed and tested a new drug delivery system that could be used to treat diseases arising from chronic inflammation.
Inflammation can be delegated either acute or chronic. Acute Inflammation is the underlying reaction of the body to destructive jolts and is accomplished by the expanded development of plasma and leukocytes (particularly granulocytes) from the blood into the harmed tissues. A course of biochemical occasions proliferates and develops the incendiary reaction, including the nearby vascular framework, the invulnerable framework and different cells inside the damaged tissue. Prolonged inflammation or chronic inflammation, prompts to a dynamic move in the kind of cells present at the site of irritation and is described by concurrent pulverization and recuperating of the tissue from the fiery procedure. Inflammatory anomalies are a huge gathering of scatters which underlie an unfathomable assortment of human maladies.
When the body’s army, its immune system begins to go rogue, disaster ensues. The double-edged sword of inflammation, which is the immune system’s first line of defense against infection, turns its destructive force onto the very body it is supposed to protect.
When short-lived, inflammation helps rid the body of invaders such as bacteria and viruses. But sometimes, damaged cells in the body can cause an immune reaction that can be longer-lasting. Since these immune reactions happen in the absence of an infection, they are called ‘sterile inflammation’ and lead to chronic conditions such as osteoarthritis, rheumatoid arthritis and fibrosis.
In a recent study, scientists from the Institute for Stem Cell Biology and Regenerative Medicine (inStem)-India, have gained new insights into how sterile inflammation can develop.
Srikala Raghavan and her team have studied how the loss of a protein called beta integrin 1 from skin cells can cause a wide-spread inflammatory reaction without the presence of invasive germs. In addition, a collaborative effort with Praveen Vemula’s group has led to the development and testing of a new drug delivery system to combat chronic inflammation.
The findings of the study appeared in Cell reports recently.
Beta integrin 1 is an essential protein on the cell surface that is involved in regulating cell shape, movement and cell reproduction. Raghavan’s team show that the loss of this molecule in the skin cells of mice results in a massive cascade of inflammatory signals that begin to recruit large numbers of immune cells. These events eventually distort the skin’s basement membrane, the tough, flexible matrix to which skin cells are anchored. However, despite widespread disarray in the basement membrane, the skin barrier remains intact.
“What’s really unique about our model is that barrier formation is completely intact in our animals – But our animals still mount a strong immune response, suggesting that the source of the inflammatory response is not external” says Raghavan pointing out that this makes the system an ideal model to study sterile inflammation. “Working out the inflammatory response from the loss of beta integrin 1 and then showing that we could alleviate this inflammation with drugs was really exciting,” she adds.
However, the immune reaction and inflammation in such mice begins to build up while they are still developing embryos in the mother. Therefore, treating the inflammation with drugs was a big challenge. “We took up the challenge of developing a very localised drug delivery vehicle,” says Praveen Vemula. “We needed to deliver the drugs transdermally, that is, into the skin,” he adds. This is where Vemula’s expertise in biomaterials came into play.
“Typically, cationic molecules – those with a positive charge – fuse with skin and can deliver cargoes inside skin. That is why we used a cationic lipid-based delivery system,” says Vemula. “What really got us excited was the efficiency of the drug delivery. We were ofcourse hoping it would work, but we expected only about 10 to 20% drug delivery. The efficiency was so high, that the outcomes of the drug treatment were plainly visible, which was a huge surprise,” he adds.
“Understanding the signals in sterile inflammation will be critical to developing targeted therapies for chronic inflammatory diseases like arthritis, Crohn’s disease and skin conditions like fibrosis, ,” say the lead authors of this publication, Ambika Kurbet and Samarth Hegde from Srikala’s team.
“Our fantastic tie-up with Praveen ensured that we were able to deliver drugs to treat the inflammation at the right place, at the right time and in the right dose in a set of very non-standard experiments,” says Srikala. “I would really like to highlight that the research environment at inStem and the collaborative atmosphere here has been critical for this work,” she adds.
There isn’t a solitary silver slug test for unending irritation. However, there are a progression of tests that, combined with your history, can give you a photo of the levels of irritation in your body. The current study teaches how to restore a healthy immune system by turning of chronic inflammation.
About the authors:
- Ambika S. Kurbet and Oindrila Bhattacharjee are affiliated to the Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, India
- Samarth Hegde was affiliated to the Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, India, while the study carried out.
- Srujan Marepally and Praveen K. Vemula are affiliated to the Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, India
- Srikala Raghavan is affiliated to the Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, India
Kurbet, Ambika S., et al. “Sterile Inflammation Enhances ECM Degradation in Integrin beta 1 KO Embryonic Skin.” Cell Reports 16(12): 3334-3347. The paper can be accessed here.