Abstract
Despite recent advances in treatment strategies, infectious diseases are still under the leading causes of death worldwide. Although the activation of the inflammatory cascade is one prerequisite of defense, persistent and exuberant immune response, however, may lead to chronicity of inflammation predisposing to a temporal or permanent tissue damage not only of the site of infection but also among different body organs. The initial response to invading pathogens is mediated by the recognition through various pattern-recognition receptors along with cellular engulfment resulting in a coordinated release of soluble effector molecules and cytokines aiming to terminate the external stimuli. Members of the ‘a disintegrin and metalloproteinase’ (ADAM) family have the capability to proteolytically cleave transmembrane molecules close to the plasma membrane, a process called ectodomain shedding. In fact, in infectious diseases dysregulation of numerous ADAM substrates such as junction molecules (e.g., E-cadherin, VE-cadherin, JAM-A), adhesion molecules (e.g., ICAM-1, VCAM-1, L-selectin), and chemokines and cytokines (e.g., CXCL16, TNF-α) has been observed. The alpha-cleavage by ADAM proteases represents a rate limiting step for downstream regulated intramembrane proteolysis (RIPing) of several substrates, which influence cellular differentiation, cell signaling pathways and immune modulation. Both the substrates mentioned above and RIPing crucially contribute to a systematic damage in cardiovascular, endocrine, and/or gastrointestinal systems. This review will summarize the current knowledge of ADAM function and the subsequent RIPing in infectious diseases (e.g., pathogen recognition and clearance) and discuss the potential long-term effect on pathophysiological changes such as cardiovascular diseases.
Highlights
Inflammation is a defensive process by which the immune system responds to an external or internal stimulus aiming to remove the injurious insult and initiate the healing process [1, 2]
The initial recognition of the pathogen occurs through germline-encoded pattern-recognition receptors (PRRs) such as the Toll-like receptors (TLRs), C-type lectin receptors, NOD-like receptors, retinoic acid-inducible gene I (RIG)-like receptors, cyclic GMP-AMP synthase and stimulator of interferon
The pathogens themselves provide pathogen-associated molecular pattern (PAMP) such as lipopolysaccharide, lipoteichoic acid, and flagellin as bacterial component as well as nucleic acids mostly associated with viral infection
Summary
Disintegrin and Metalloproteinase—Control Elements in Infectious Diseases. Despite recent advances in treatment strategies, infectious diseases are still under the leading causes of death worldwide. In infectious diseases dysregulation of numerous ADAM substrates such as junction molecules (e.g., E-cadherin, VE-cadherin, JAM-A), adhesion molecules (e.g., ICAM-1, VCAM-1, L-selectin), and chemokines and cytokines (e.g., CXCL16, TNF-α) has been observed. The alpha-cleavage by ADAM proteases represents a rate limiting step for downstream regulated intramembrane proteolysis (RIPing) of several substrates, which influence cellular differentiation, cell signaling pathways and immune modulation. Both the substrates mentioned above and RIPing crucially contribute to a systematic damage in cardiovascular, endocrine, and/or gastrointestinal systems.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
