Beyond Macromolecules: Extracellular Vesicles as Regulators of Inflammatory Diseases

Abstract

Inflammation is the defense mechanism of the immune system against harmful stimuli such as pathogens, toxic compounds, damaged cells, radiation, etc., and is characterized by tissue redness, swelling, heat generation, pain, and loss of tissue functions. Inflammation is essential in the recruitment of immune cells at the site of infection, which not only aids in the elimination of the cause, but also initiates the healing process. However, prolonged inflammation often brings about several chronic inflammatory disorders; hence, a balance between the pro- and anti-inflammatory responses is essential in order to eliminate the cause while producing the least damage to the host. A growing body of evidence indicates that extracellular vesicles (EVs) play a major role in cell–cell communication via the transfer of bioactive molecules in the form of proteins, lipids, DNA, RNAs, miRNAs, etc., between the cells. The present review provides a brief classification of the EVs followed by a detailed description of how EVs contribute to the pathogenesis of various inflammation-associated diseases and their implications as a therapeutic measure. The latter part of the review also highlights how EVs act as a bridging entity in blood coagulation disorders and associated inflammation. The findings illustrated in the present review may open a new therapeutic window to target EV-associated inflammatory responses, thereby minimizing the negative outcomes.

Role of MCP-1 as an inflammatory biomarker in nephropathy

“…It is noteworthy that this study presents innovative findings regarding the association between plasma MCP-1 levels and the progression of DN in patients with moderate to severe CKD ( 55 ). Extracellular vesicles (EVs), which encompass exosomes and microvesicles, play a vital role in facilitating intercellular communication by transporting biomolecules like mRNA ( 56 ). The investigation focused on MCP-1 mRNA expression within blood EVs of patients with DN to determine its accuracy in predicting the early stages of DN.…”

Coagulation Protease-Driven Cancer Immune Evasion: Potential Targets for Cancer Immunotherapy

“…PAR2-mediated human breast cancer progression also occurs through indirect mechanisms. TF/FVIIa/PAR2 signaling induces the release of nano-sized microvesicles (MVs) from human highly metastatic breast cancer cells [93], which are enriched with microRNA221 (miR-221), and the MV-mediated transfer of miR-221 confers proliferative, metastatic, and anti-apoptotic potential to non-metastatic breast cancer cells via the induction of EMT [85,94]. PAR2 activation via another protease, trypsin, also induces pro-metastatic MV generation from metastatic breast cancer cells, imparting metastatic potential to non-metastatic breast cancer cells [95].…”

The intersection of coagulation activation and inflammation after injury: What you need to know

“…Extracellular vesicles include exosomes, microvesicles, and apoptotic bodies. Originally thought to be inert, it is now recognized that EVs contain proteins, lipids, metabolites, and nucleic acids from the parent cell and serve a role in cell-cell communication and inflammatory signaling 88–90 . The systemic inflammatory response after injury or sepsis appears to cause EV release into the circulation, 91 although the cellular source and downstream effects have yet to be defined 92,93 .…”