Particulate matter with a diameter ≤2.5 μm (PM_2.5) poses a substantial global challenge, with a growing recognition of pathogens contributing to diseases associated with exposure to PM_2.5. Recent studies have focused on PM_2.5, which impairs the immune cells in response to microbial infections and potentially contributes to the development of severe diseases in the respiratory tract. Accordingly, changes in the respiratory immune function and microecology mediated by PM_2.5are important factors that enhance the risk of microbial pathogenesis. These factors have garnered significant interest. In this review, we summarise recent studies on the potential mechanisms involved in PM_2.5-mediated immune system disruption and exacerbation of microbial pathogenesis in the respiratory tract. We also discuss crucial areas for future research to address the gaps in our understanding and develop effective strategies to combat the adverse health effects of PM_2.5.

Cytolethal distending toxin (CDT), one of the most important genotoxins, is produced by several gram-negative bacteria and is involved in bacterial pathogenesis. Recent studies have shown that bacteria producing this peculiar genotoxin target host DNA, which potentially contributes to development of cancer. In this review, we highlighted the recent studies focusing on the idea that CDT leads to DNA damage, and the cells with inappropriately repaired DNA continue cycling, resulting in cancer development. Understanding the detailed mechanisms of genotoxins that cause DNA damage might be useful for targeting potential markers that drive cancer progression and help to discover new therapeutic strategies to prevent diseases caused by pathogens.

Berberine is an isoquinoline alkaloid isolated from various Chinese herbs that has potential of anti-inflammatory, anti-lipidemic, anti-neoplastic, and anti-diabetic activity. In this study, we evaluated the anti-inflammatory efficacy of berberine on allergic airway inflammation by targeting epithelial cells. Allergic airway inflammation driven by T helper 2 (Th2)-type immunity is characterized by airway hyperresponsiveness, elevated IgE production, and eosinophilic infiltration. For eosinophil recruitment, major chemoattractant CCL11 (eotaxin-1) was secreted by lung epithelial cells. BEAS-2B cells, a human bronchial epithelial cell line, were pre-treated with berberine and then activated by IL-4 plus TNF-α. The viability of BEAS-2B cells was assessed. Expression levels of IL-6 and CCL11 were determined using ELISA and real-time PCR. The signaling pathways of MAP kinases, NF-κB, and STAT6 were analyzed by western blot. Berberine treatment (≤1 μM) didn't significantly affect the viability of BEAS-2B cells with or without IL-4 plus TNF-stimulation. Berberine significantly inhibited the secretion of IL-6 and CCL11 from pro-inflammatory cytokine-activated BEAS-2B cells. NF-κB and MAP kinase pathways were seemingly unaffected in BEAS-2B cells with berberine treatment. Significant reduction of nuclear STAT6 protein expression in activated BEAS-2B cells with berberine treatment was observed. Current study reveals that berberine has inhibitory effect in pro-inflammatory cytokine-activated BEAS-2B cells through reducing IL-6 and CCL11 production, which is possibly modulated by suppressing STAT6 signaling pathway.

The "master transcription factor" FOXP3 regulates the differentiation, homeostasis, and suppressor function of CD4+ regulatory T (Treg) cells, which are critical in maintaining immune tolerance. Epigenetic regulation of FOXP3 expression has been demonstrated to be important to Treg cell development, but the induction of human Treg cells through epigenetic modification has not been clearly described. We report that the combination of the DNA methyltransferase inhibitor 5-azacytidine (5-Aza) and suboptimal T cell receptor (TCR) stimulation promoted CD4+CD25hFOXP3+ T cell induction from human CD4+CD25- T cells. 5-Aza treatment enhanced the expression of Treg cell signature genes, CD25, FOXP3, CTLA-4, and GITR, in CD4+CD25h cells. Moreover, 5-Aza-treated CD4+CD25h T cells showed potent suppressive activity in a cell contact-dependent manner and reduced methylation in the Treg-specific demethylated region (TSDR) in the FOXP3 gene. The analysis of cytokine production revealed that CD4+CD25- T cells with 5-Aza treatment produced comparable levels of interferon (IFN)-γ and transforming growth factor (TGF)-β, but less IL-10, and more IL-2 when compared to cells without 5-Aza treatment. The increased IL-2 was indispensible to the enhanced FOXP3 expression in 5-Aza-treated CD4+CD25h cells. Finally, 5-Aza-treated CD4+CD25h T cells could be expanded with IL-2 supplementation alone and maintained FOXP3 expression and suppressor function through the expansion. Our findings demonstrate that DNA demethylation can enhance the induction of human Treg cells and promise to solve one of the challenges with using Treg cells in therapeutic approaches.

Exposure to particulate matter (PM) has been associated with DNA damage, but the relationships between PM, telomere length and cellular senescence remain unclear. This study aimed to investigate the effects and potential mechanisms of PM on telomere length and cellular senescence in human lung epithelial cells. Human lung epithelial A549 cells were exposed to PM for 24 h. Cell viability and cytotoxicity were measured by the WST-1 assay and the lactate dehydrogenase release, respectively. Cellular uptake of PM was observed using transmission electron microscopy. Telomere length was measured using qPCR and expressed as T/S ratio. Cell cycle progression was analyzed by flow cytometry. Expression of human telomerase reverse transcriptase (hTERT) and cell cycle regulators was measured using mRNA by qPCR and protein levels by Western blot. Cellular senescence was determined by the expression of senescence-associated β-galactosidase (SA-β-Gal) with fluorescent microscopy and flow cytometry. Exposed to PM at the concentration of 200 μg/ml decreased cell viability and increased LDH levels in culture medium. Remarkably increased uptake of PM, shortening of telomere length, induction of G0/G1 phase arrest, and increased expression of senescence hallmarks were observed after exposure to PM in A549 cells. PM exposure induced upregulation of p21 and downregulation of proliferating cell nuclear antigen (PCNA) and hTERT expression, but no significant change in p53 expression, in A549 cells. Overall, exposure to PM may downregulate hTERT and PCNA through p53-independent induction of p21 expression, leading to telomere shortening, G0/G1 arrest and the onset of cellular senescence in human lung epithelial cells.