Phosphodiesterase type 5 inhibitor tadalafil reduces prostatic fibrosis via MiR-3126-3p/FGF9 axis in benign prostatic hyperplasia.

Myofibroblast buildup and prostatic fibrosis play a crucial role in the development of benign prostatic hyperplasia (BPH). Treatments specifically targeting myofibroblasts could be a promising approach for treating BPH. Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, holds the potential to intervene in this biological process. This study employs prostatic stromal fibroblasts to induce myofibroblast differentiation through TGFß1 stimulation. As a result, tadalafil significantly inhibited prostatic stromal fibroblast proliferation and fibrosis process, compared to the control group. Furthermore, our transcriptome sequencing results revealed that tadalafil inhibited FGF9 secretion and simultaneously improved miR-3126-3p expression via TGFß1 suppression. Overall, TGFß1 can trigger pro-fibrotic signaling through miR-3126-3p in the prostatic stroma, and the use of tadalafil can inhibit this process.

House dust mite exposure enhances immune responses to ovalbumin-induced intestinal allergy.

House dust mites (HDM) are one of the important factors of airway allergic diseases, HDM allergens can be detected in the human gut mucosa, which induces local inflammation and increases intestinal epithelial permeability. This study tests a hypothesis that HDM contribute to the development of OVA (ovalbumin)-induced intestinal allergy. The serum levels of IgE against HDM in patients with food allergy were detected with UniCAP100 (Pharmacia, Uppsala, Sweden); a mouse model of food allergy was developed with OVA and HDM as the specific antigens. Compared to healthy controls, patients with food allergy have higher levels of serum HDM-specific IgE. Compared to food allergy alone groups, the levels of HDM-specific IgE in patients with food allergy and asthma or allergic rhinitis were significantly higher. In mouse models, we found that HDM/OVA induced allergy-like symptoms, lower body temperature, and lower body weight. The levels of IgE, IgG1, mMCP-1 (mouse mast cell protease-1), IL-4 and IL-5 in the HDM and HDM + CT (cholera toxin) groups were higher than the control groups, and the levels of IgE, IgG1, IL-4 and IL-5 in the HDM, OVA and HDM + OVA groups were higher than the control groups. The pathological changes of intestinal tissues in the HDM and HDM + CT/the HDM, OVA and HDM + OVA groups were more severe, more eosinophil infiltration than the control groups. Moreover, exposure to HDM induced intestinal barrier dysfunction, and facilitated the development of intestinal allergy in mice. In conclusion, HDM exposure enhances immune responses to OVA-induced food allergy.

Dust-mite-derived protein disulfide isomerase suppresses airway allergy by inducing tolerogenic dendritic cells.

House dust mites (HDMs) are a potent allergen source that are commonly found in human living environments. While HDMs are known to induce allergic diseases in humans, such as asthma, its other biological activities related to human health are less understood. Our laboratory recently purified the HDM protein PDI (protein disulfide isomerase). In this study, we assess the role of PDI in contributing to immune regulation. Using mass spectrometry, we analyzed the complexes of DEC205 and HDM extracts, and the role of PDI in the induction of tolerogenic dendritic cells (DCs) was assessed in human cell culture experiments and verified in a murine model. We found that more than 20 HDM-derived proteins, including PDI, bound to DCs by forming complexes with DEC205. Additionally, DEC205-mediated the endocytosis of PDI. HDM-derived PDI (HDM-PDI) promoted Foxp3 expression in DCs. HDM-PDI-primed DCs also showed tolerogenic properties that induced regulatory T cell development, indicating that the primed DCs were tolerogenic DCs. Our results suggested that the PDI/DEC205/TIEG1/Foxp3 signal pathway activation was involved in the HDM-PDI-induced Foxp3 expression in DCs. Finally, we found that HDM-PDI competitively counteracted the Th2 cytokines to restore DC's tolerogenicity, and administration of HDM-PDI could suppress experimental asthma. In conclusion, our data suggest that HDM-PDI contributes to immune regulation by inducing tolerogenic DC development. Administration of HDM-PDI can alleviate experimental asthma. These findings demonstrate that HDM-PDI has translational potential to be used in the treatment of immune disorders such as asthma.

Cross-reactive antibodies against dust mite-derived enolase induce neutrophilic airway inflammation.

BACKGROUND AND AIMS: Neutrophilic inflammation is a hallmark of some specific asthma phenotypes; its aetiology is not yet fully understood. House dust mite (HDM) is the most common factor in the pathogenesis of airway inflammation. This study aims to elucidate the role of cross-antibodies against HDM-derived factors in the development of neutrophilic inflammation in the airway. METHODS: Blood samples were collected from asthma patients with chronic neutrophilic asthma for analysis of HDM-specific cross-reactive antibodies. The role of an antibody against HDM-derived enolase (EnoAb) in the impairment of airway epithelial barrier function and induction of airway inflammation was assessed in a cell culture model and an animal model. RESULTS: High similarity (72%) of the enolase gene sequences was identified between HDM and human. Serum EnoAb was detected in patients with chronic neutrophilic asthma. The EnoAb bound to airway epithelial cells to form complexes with enolase, which activated complement, impaired airway epithelial barrier functions and induced neutrophilic inflammation in the airway tissues. CONCLUSIONS: HDM-derived enolase can induce specific cross-antibodies in humans, which induce neutrophilic inflammation in the airway.