Now, researchers from the Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bengaluru have, for the first time, identified that the loss of a protein called beta integrin 1 from skin cells causes widespread inflammatory reaction, which triggers such diseases.
The finding is important as beta integrin 1 is an essential protein on the cell surface that is involved in regulating cell shape, movement, growth and cell division. It is also important in developing targeted therapies for chronic inflammatory diseases, said the research team.
“When a virus attacks the body’s immune system, inflammation is the first line of defence, which rids the body of pathogens such as bacteria and viruses. However, sometimes, damaged cells in the body elicit 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 can cause chronic conditions such as osteoarthritis, rheumatoid arthritis, fibrosis and Crohn’s disease. We have now discovered that the loss of beta-1 protein can lead to similar mechanisms making this animal model extremely important to understand most of these diseases,” lead author of the study from inStem, Ambika Kurbet, told Bangalore Mirror.
The findings have been reported in the journal Cell Reports.
She said the loss is from the epidermis or the outer layer of the skin, and owing to this, the cells of body sense stress. This causes several diseases, she said, adding that it is also responsible for skin disorders like atopic dermatitis and hyper-sensitive skin, all with an inflammatory component.
The team found that the immune reaction and inflammation in mice begins to build up while they are still developing embryos in the mother.
“We have demonstrated that the loss of this protein in the skin cells of mice results in a massive cascade of inflammatory signals that begin to recruit large numbers of immune cells. This means that the body’s immune response starts over-responding and it does not shut down, leading to chronic state of inflammation. Another interesting observation to highlight is the skin barrier is completely formed, ruling out external agents to be the cause of inflammation. These events eventually distort and degrade the skin’s basement membrane, the tough, flexible matrix to which skin cells are anchored,” said Kurbet.
They explored several methods of preventing this inflammation through different inhibitors. Since the condition was seen in the embryonic stage itself, inhibitors had to be delivered early in development. To tackle this problem, the team collaborated with Dr Praveen Vemula’s laboratory of self-assembled biomaterials at inStem, which has led to the development and testing of a new drug delivery system to combat chronic inflammation. This is a very localised drug delivery vehicle that delivers drug transdermally, that is, into the skin. The team had to develop two different types of drug delivery systems, one to carry small-molecule drugs and the other to carry antibodies. Another condition the delivery system had to meet was slow release of the carried drug over a period of several days. “We took up the challenge of developing a very localised drug delivery vehicle. What was really exciting was the efficiency of the drug delivery. We were hoping it would work, but we expected only about 10 to 20 per cent drug delivery. The efficiency was so high, that the results of the drug treatment were plainly visible, which was a surprise,” said the research team.