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Exosomes are nanosized vesicles and have recently been recognized as important players in cell-to-cell communication. Exosomes contain different mediators such as proteins, nucleic acids (DNA, mRNA, miRNAs, and other ncRNAs), and lipid mediators and can shuttle their exosomal content to both neighboring and distal cells. Exosomes are very effective in orchestrating immune responses in the airways and all cell types can contribute to the systemic exosome pool. Intracellular communication between the broad range of cell types within the lung is crucial in disease emphasizing the importance of exosomes. In asthma, exosomes affect the inflammatory microenvironment which ultimately determines the development or alleviation of the pathological symptoms. Recent studies in this area have provided insight into the underlying mechanisms of disease and led to interest in using exosomes as potential novel therapeutic agents. [ABSTRACT FROM AUTHOR]

Cystic Fibrosis (CF) is the most common lethal autosomal recessive disease that affects many organs including, lung, pancreas and liver. Cystic fibrosis is a monogenic disease and occurs in the white Caucasians. Massive neutrophil granulocyte influx in the airways is one of the characteristics of CF. Extracellular Vesicles (EVs), microvesicles, and exosomes are vesicles released from cells into extracellular space of the body and are able to influence other cells by different methods. They have an important role in the intracellular communication by transferring information between donor and recipients cells. Granulocytes are known as the main source of microparticles in the CF patients. Microparticles derived from neutrophils are associated with the extensive neutrophil influx into airways and aggregation at the epithelial surface of the CF patient's respiratory tract. Exosomes are found in almost all body fluids, such as urine, sputum, Bronchoalveolar Lavage (BAL), milk, Cerebrospinal Fluid (CSF), plasma and sputum. Examination of exosomes derived from CF patients may be helpful in the characterization of pathogenesis of disease in detail. In this mini review, we have summarized the role of microparticles and exosomes in pathogenesis of CF and finally discussed the feasibility of this particle in treatment approaches. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) remains a significant global health concern and its diagnosis is challenging due to the limitations in the specificity and sensitivity of the current diagnostic tests. Exosomes are bioactive 30-100 nm vesicles produced by most cell types and are found in almost all human body fluids. Exosomal microRNAs (miRNAs) can transfer biological information between cells and tissues and may act as potential biomarkers in many diseases. In this pilot study, we assessed the miRNA profile of exosomes released from human monocyte-derived macrophages upon infection with Mycobacterium bovis Bacillus Calmette-Guerin (BCG).Methods: Human monocytes were obtained from the peripheral blood of three healthy subjects and driven to a monocyte-derived macrophage (MDM) phenotype using standard protocols. MDMs were infected with BCG or left uninfected as control. 72 h post-infection, exosomes were collected from the cell culture medium, RNA was isolated and RNA-seq performed. The raw reads were filtered to eliminate adaptor and primer sequences and the sequences were run against the mature human miRNA sequences available in miRBase. MicroRNAs were identified using an E value <0.01. miRNA network analysis was performed using the DIANA miRNA tool, miRDB and functional KEGG pathway analysis.Results: Infection of MDMs with BCG leads to the release of several exosomal miRNAs. These included miR-1224, -1293, -425, -4467, -4732, -484, -5094, -6848-6849, -4488 and -96 all of which were predicted to target metabolism and energy production-related pathways.Conclusions: This study provides evidence for the release of specific exosomal miRNAs from BCG-infected MDMs. These exosomal miRNAs reflect host-pathogen interaction and subversion of host metabolic processes following infection. [ABSTRACT FROM AUTHOR]

Exosomes are nanosized vesicles released from every cell in the body including those in the respiratory tract and lungs. They are found in most body fluids and contain a number of different biomolecules including proteins, lipids, and both mRNA and noncoding RNAs. Since they can release their contents, particularly miRNAs, to both neighboring and distal cells, they are considered important in cell-cell communication. Recent evidence has shown their possible importance in the pathogenesis of several pulmonary diseases. The differential expression of exosomes and of exosomal miRNAs in disease has driven their promise as biomarkers of disease enabling noninvasive clinical diagnosis in addition to their use as therapeutic tools. In this review, we summarize recent advances in this area as applicable to pulmonary diseases. [ABSTRACT FROM AUTHOR]

Our knowledge of the role of innate immunity in protecting against cancers has expanded greatly in recent years. An early focus was on the adoptive transfer of natural killer (NK) cells and, although this approach has demonstrated promising results in many patients, a few limitations including immune escape of tumors from cytotoxic killing by NK cells have caused treatment failures. Downregulation of the expression of activating ligands on the surface of cancer cells and prevention of the activity of soluble factors are among the mechanisms employed by cancer cells to overcome NK-mediated immunity. It has become evident that a class of small membranous structures of endosomal origin known as exosomes play a key role in regulating the local tumor microenvironment. Here we hypothesize that exosome secretion by cancer cells, which is greater than that of normal cells, is an important escape mechanism employed by cancer cells. Interruption of exosome release by various inhibitory agents in combination with the adoptive transfer of NK cells may overcome, at least in part, the treatment failures that occur with adoptive NK cell transfer. In this regard, repositioning of approved drugs with previously shown effects on exosome release may be a good strategy to bypass the safety issues of newly identified agents and will also dramatically reduce the huge costs of drug approval process. [ABSTRACT FROM AUTHOR]

Background: Despite the advances in the treatment of multiple myeloma (MM), complete remission is usually challenging. The interactions between tumor and host cells, in which exosomes (EXs) play critical roles, have been shown to be among the major deteriorative tumor-promoting factors herein. Therefore, any endeavor to beneficially target these EX-mediated interactions could be of high importance. Objectives: a) To investigate the effects of myeloma EXs on natural killer (NK) cell functions. b) To check whether treatment of myeloma cells with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), two polyunsaturated omega-3 fatty acids with known anti-cancer effects, can modify myeloma EXs in terms of their effects on natural killer functions. Methods: L363 cells were treated with either EPA or DHA or left untreated and the released EXs (designated as E-EX, D-EX and C-EX, respectively) were used to treat NK cells for functional studies. Results: Myeloma EXs (C-EXs) significantly reduced NK cytotoxicity against K562 cells (P ≤ 0.05), while the cytotoxicity suppression was significantly lower (P ≤ 0.05) in the (E-EX)- and (D-EX)-treated NK cells compared to the (C-EX)-treated cells. The expression of the activating NK receptor NKG2D and NK degranulation, after treatment with the EXs, were both altered following the same pattern. However, C-EXs could increase IFN-γ production in NK cells (P < 0.01), which was not significantly affected by EPA/DHA treatment. This indicates a dual effect of myeloma EXs on NK cells functions. Conclusion: Our observations showed that myeloma EXs have both suppressive and stimulatory effects on different NK functions. Treatment of myeloma cells with EPA/DHA can reduce the suppressive effects of myeloma EXs while maintaining their stimulatory effects. These findings, together with the previous findings on the anti-cancer effects of EPA/DHA, provide stronger evidence for the repositioning of the currently existing EPA/DHA supplements to be used in the treatment of MM as an adjuvant treatment. [ABSTRACT FROM AUTHOR]

Introduction. Tuberculosis (TB) remains a major threat to human health. Due to the limited accuracy of the current TB diagnostic tests, it is critical to determine novel biomarkers for this disease. Circulating exosomes have been used as diagnostic biomarkers in various diseases. Objective of the Study. In this pilot study, we examined the expression of miRNAs as biomarker candidates for the diagnosis of TB infection. Methods. Serum-derived exosomes were isolated from TB patients and matched control subjects. The expression of miR-484, miR-425, and miR-96 was examined by RT-PCR methods. Results. The expression of miR-484, miR-425, and miR-96 were significantly increased in serum of TB patients which correlated with the TB infection level. A receiver operating characteristic (ROC) curve analysis showed the diagnostic potency of each individual serum exosomal miRNA with an area under the curve AUC=0.72 for miR-484 (p<0.05), 0.66 for miR-425 (p<0.05), and 0.62 for miR-96 (p<0.05). Conclusion. These results demonstrate that exosomal miRNAs have diagnostic potential in active tuberculosis. The diagnostic power may be improved when combined with conventional diagnostic markers. [ABSTRACT FROM AUTHOR]