Several studies show that childhood and adulthood asthma and its symptoms can be modulated through epigenetic modifications. Epigenetic changes are inheritable modifications that can modify the gene expression without changing the DNA sequence. The most common epigenetic alternations consist of DNA methylation and histone modifications. How these changes lead to asthmatic phenotype or promote the asthma features, in particular by immune pathways regulation, is an understudied topic. Since external effects, like exposure to tobacco smoke, air pollution, and drugs, influence both asthma development and the epigenome, elucidating the role of epigenetic changes in asthma is of great importance. This review presents available evidence on the epigenetic process that drives asthma genes and pathways, with a particular focus on DNA methylation, histone methylation, and acetylation. We gathered and assessed studies conducted in this field over the past two decades. Our study examined asthma in different aspects and also shed light on the limitations and the important factors involved in the outcomes of the studies. To date, most of the studies in this area have been carried out on DNA methylation. Therefore, the need for diagnostic and therapeutic applications through this molecular process calls for more research on the histone modifications in this disease.

Background A complex community of microorganisms in the gastrointestinal (GI) tract, known as the gut microbiota, exerts major effects on gene expression and cytokine profile. Extracellular vesicles (EVs) which are produced by bacteria could be sensed by Toll like receptors (TLRs). The interaction between gut microbiota and TLRs affects homeostasis and immune responses. In this study, we evaluated TLR9 gene expression and cytokines level in Caco-2 cell line treated with Lactobacillus casei as one of the gut microbiota and its EVs. Methods In the present study, L. casei derived EVs was extracted via ultracentrifugation. The quality control assessment included the evaluation of physicochemical characteristics of EVs. For the treatment of Caco-2 cell line, L. casei and its EVs (100 and 150 μg/mL) were used. In addition, qRT-PCR assay was carried out to evaluate the mRNA expression of TLR9 gene. ELISA assay was also performed to determine the levels of IFN γ , TNF-α, GM-CSF, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-12, IL-17A, and IL-10 cytokines.Results The results showed that L. casei slightly increased TLR9 gene expression in the Caco-2 cell line. It was also found that EVs at concentrations of 100 and 150 μg/mL could significantly decrease TLR9 gene expression. Furthermore, L. casei significantly increased IL-10 and IFN γ levels. Based on the findings, the level of IL-17A, as a proinflammatory cytokine, decreased by L. casei. Both concentrations of EVs decreased the level of IFN γ , while increasing the concentrations of IL-4 and IL-10. EVs from L. casei could modulate immune responses in the Caco-2 cell line. Both EVs and L. casei activated the expression and secretion of several cytokines. Conclusions L. casei and its EVs have pivotal role in the cross talk between gut microbiota and the host especially in the modulation of the immune system. This study shows for the first time the increasing level of anti-inflammatory cytokines by EVs released by L. casei. Based on the last studies on immunomodulatory effect of EVs on immune cells and our results in cell line level, we postulate that L. casei derived EVs could be possible candidates for the reduction of immune responses.

Extracellular vesicles are nanoscale particles which were identified about fifty years ago. The studies have shown that all of the gram-negative bacteria secrete extracellular vesicles during their normal growth. Today, the production of membrane vesicles has been reported by gram-positive bacteria, parasites, fungi, and mycobacteria. Since these nanoscale particles carry many of the bacterial components such as DNA, RNA, protein, endotoxin, and virulence molecules, they play a very important role in interacting with the environment and other bacteria. For this reason, many of these vesicles are considered as the transmission of pathogens, antigenic protein compounds, and the development of non-cellular vaccines, as well as drug delivery agents. The studies, have been carried in this field so far, have been focused on the pathogenic and physiological roles of these nanostructures in cross-species relationships. The focus of this article is on the role of extracellular bacterial vesicles and pathological and physiological functions which contribute to the interactions between bacteria and bacteriumhost. Since these nanostructures play significant role in pathogenesis, gene transduction, regulation of gene expression, immune response regulation, and cellular signaling, further studies are needed on the medical application of these nanostructures as a new generation of vaccines, adjuvants, drug delivery agents.

Introduction The secretion of extracellular vesicles (EVs) has been neglected in Gram-positive bacteria due to the absence of an outer membrane and the difficulties of proper visualization. Here we aimed to prove that lactobacillus casei can secrete extracellular vesicles. Methods: EVs were extracted from Lactobacillus casei, cultured in De Man, Rogosa and Sharpe broth, using a polyethylene glycol (PEG) solution. The characteristics of the EVs were analyzed by electron microscopy, Dynamic Light Scattering (DLS) and SDS-PAGE. Results: The electron microscopy showed rounded vesicles with average diameter of 300 nm. The protein content of this nanostructure was 2.5 mg/ml with a protein pattern within the range of 10-200 kDa. DLS result showed populations of approximately 300 nm while the extracted EVs had a negative zeta potential. Conclusion: A new method of producing functional molecules from probiotic bacteria was presented. Our results indicated EVs purity with acceptable conformation. Further investigations are necessary to elucidate the efficacy, practicality and mechanism of action of such EVs in clinical practices, especially for development of bio-compounds and vaccine delivery vehicles.