Indian Institute of Technology researchers have identified a new immunomodulatory function of a protein that could potentially help in treating sepsis and other inflammatory diseases caused by abnormal functions of immune cells
Elaborating on the importance of this work, the lead researcher Dr Pranita P Sarangi, Assistant Professor, Department of Biotechnology, IIT Roorkee, said, “Abnormal functions of immune cells are associated with many pathological conditions such as severe sepsis (blood infection) and other inflammatory diseases. During sepsis, an uncontrolled infection leads to abnormal activation and localiSation of important immune cells such as neutrophils and macrophages.”
In an animal model of sepsis, both the full length Fbln7 (Fbln7-FL) protein and its C-terminal fragment (Fbln7C) inhibited macrophage and neutrophil infiltration to the inflamed tissues and organs such as peritoneal cavity and lungs. This data demonstrates that Fbln7 and its bioactive fragments or shorter peptides may have therapeutic potential for treating immuno-pathological conditions, which require negative regulation of immune cell functions. Currently, further research is going on this aspect in the laboratory.
Dr Sarangi said, “Our immune system consists of varieties of white blood cells (WBCs) or leukocytes. In response to any inflammatory and infectious stimulus, leukocytes travelling in the blood vessels immediately respond by migrating to the affected site. While exiting the blood vessel and further travelling through the tissue spaces, activated WBCs interact with extracellular matrix proteins such as collagen, fibronectin etc. The immune cells bind to such proteins via their surface receptor molecules called as integrins. These cell matrix communication through integrin receptors not only provide support for migration but also modulate various functions of the immune cells. Recently, therapeutics targeting integrins and associated molecules have been approved for clinical trials in many diseases such as cancers (e.g. RGD peptide).”
Fibulin-7 (Fbln7) was identified as the latest member of the fibulin family in developing tooth, functioning as a cell adhesion molecule and has the ability to interact with other matrix proteins, receptors, and growth factors. In this study using human peripheral blood monocytes and an endotoxin induced systemic inflammation mouse model, researchers showed that Fbln7 and its C-terminal fragment could inhibit adhesion, migration and production of inflammatory molecules from monocytes and macrophages.
The research team consisted of Dr Sarangi, Dr Kiran Ambatipudi, Ms Papiya Chakraborty and Mr Shiba Prasad Dash from the Department of Biotechnology, IIT Roorkee, while Dr Yoshihiko Yamada’s team from National Institutes of Health, USA. This research work was funded by faculty initiation grant from IIT Roorkee and young scientist research grant from the Department of Science and Technology, Govt. of India to Dr Sarangi, while Dr Yamada was funded through intramural grant from National Institutes of Health, USA.
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