Search

Neutrophil infiltration is frequently observed in lung cancer tissues. Extracellular RNAs (exRNAs) may facilitate tumor progression. The present study investigated the cross‑talk of tumor exRNAs and neutrophil extracellular traps (NETs) in lung cancer. Lewis lung carcinoma (LLC) cells were cultured with the deprived sera. And the cell culture supernatants (CCS) were analyzed in vitro and in vivo. The results revealed that exRNAs from lung cancer CCS promoted the inflammatory cytokine interleukin‑1β and reduced the vascular cell adhesion molecule‑1 expression in lung epithelial cells. Lung cancer CCS‑treated epithelial cells induced the production of NETs. By contrast, NETs reduced the tight junction protein claudin‑5 in epithelial cells. Furthermore, NETs caused the necrosis of epithelial cells, which resulted in the release of exRNAs. In mice, lung cancer cells instilled in the lung recruited neutrophils and initiated NETs. In patients with lung cancer, NETs were also observed. These results suggested that exRNAs in the cell culture supernatant may indirectly induce NETs and contribute to lung cancer oncogenesis.

Cryptococcus neoformans (C. neoformans) is an important opportunistic fungal pathogen for pulmonary cryptococcosis. Previously, we demonstrated that CD146 mediated the adhesion of C. neoformans to the airway epithelium. CD146 is more than an adhesion molecule. In the present study, we aimed to explore the roles of CD146 in the inflammatory response in pulmonary cryptococcosis. CD146 was decreased in lung tissues from patients with pulmonary cryptococcosis. Similarly, C. neoformans reduced pulmonary CD146 expression in mice following intratracheal inoculation. To explore the pathological roles of CD146 reduction in pulmonary cryptococcosis, CD146 knockout (KO) mice were inoculated with C. neoformans via intratracheal instillation. CD146 deficiency aggravated C. neoformans infection, as evidenced by a shortened survival time and increased fungal burdens in the lung. Inflammatory type 2 cytokines (IL-4, IL-5, and TNF-α) and alternatively activated macrophages were increased in the pulmonary tissues of CD146 KO-infected mice. CD146 is expressed in immune cells (macrophages, etc.) and nonimmune cells, i.e., epithelial cells and endothelial cells. Bone marrow chimeric mice were established and infected with C. neoformans. CD146 deficiency in immune cells but not in nonimmune cells increased fungal burdens in the lung. Mechanistically, upon C. neoformans challenge, CD146 KO macrophages produced more neutrophil chemokine KC and inflammatory cytokine TNF-α. Meanwhile, CD146 KO macrophages decreased the fungicidity and production of reactive oxygen species. Collectively, C. neoformans infection decreased CD146 in pulmonary tissues, leading to inflammatory type 2 responses, while CD146 deficiency worsened pulmonary cryptococcosis. [ABSTRACT FROM AUTHOR]

Background: The microtubule-dependent molecular motor protein Kinesin Family Member 2A (KIF2A) is down-regulated in asthmatic human airway epithelium. However, little is known about the roles of KIF2A as well as the possible underlying mechanisms in asthma. Methods: House dust mite (HDM) extract was administered to establish a murine model of asthma. The expression of KIF2A, IL-33 and the autophagy pathways were detected. The plasmid pCMV-KIF2A was used to overexpress KIF2A in the airway epithelial cells in vitro and in vivo. IL-4, IL-5, IL-33 and other cytokines in bronchoalveolar lavage fluid (BALF) and lung tissues homogenates were measured. Results: In response to the challenge of house dust mite (HDM) in vitro and in vivo, airway epithelial cells displayed decreased production of KIF2A. Meanwhile, autophagy and IL-33 were increased in HMD-treated epithelial cells. Mechanistically, KIF2A decreased autophagy via suppressing mTORC1 pathway in HDM-treated epithelial cells, which contributed to the reduced production of IL-33. Moreover, in vivo KIF2A transfection reduced IL-33 and autophagy in the lung, leading to the attenuation of allergic asthma. Conclusion: KIF2A suppressed mTORC1-mediated autophagy and decreased the production of epithelial-derived cytokine IL-33 in allergic airway inflammation. These data indicate that KIF2A may be a novel target in allergic asthma. [ABSTRACT FROM AUTHOR]

Objective: The IL‐33/ST2 axis has been extensively investigated in type 2 eosinophilic inflammation. Here, we aimed to investigate the role of the IL‐33/ST2 axis in neutrophil‐dominant allergic airway inflammation. Methods: House‐dust mite (HDM) extract and lipopolysaccharide (LPS) were administered to establish a murine model of neutrophil‐dominant allergic airway inflammation. The formation of neutrophilic extracellular traps (NETs) in the lung tissues was demonstrated by immunofluorescence imaging. Mature IL‐33 in bronchoalveolar lavage fluid (BALF) was detected by Western blotting. The neutrophilic chemokine KC produced by bone marrow‐derived macrophages (BMDMs) or primary alveolar epithelial cells was measured with a commercial ELISA kit. Results: In the present study, we observed neutrophilic inflammation and tight junction damage in the lungs of mice sensitised with HDM and LPS. Furthermore, sensitisation with HDM and LPS resulted in the formation of NETs, accompanied by increased levels of mature IL‐33 in the BALF. Moreover, LPS damaged the epithelial tight junction protein occludin directly or indirectly by inducing NET formation. Surprisingly, IL‐33 deficiency augmented neutrophilia and epithelial barrier injury in the lungs of mice after sensitisation with HDM and LPS. Similarly, the absence of ST2 exacerbated the neutrophilic inflammatory response, decreased the expression of occludin and exacerbated the severity of neutrophil‐dominant allergic airway inflammation in an HDM/LPS‐induced mouse model. Mechanistically, BMDMs and alveolar epithelial cells from IL‐33‐ or ST2‐deficient mice tended to produce higher levels of the neutrophilic chemokine KC. Conclusions: These results demonstrated that the IL‐33/ST2 axis may play a protective role in neutrophil‐dominant allergic airway inflammation. [ABSTRACT FROM AUTHOR]

Air pollution is a leading cause of increasing infectious lung diseases. Pulmonary cryptococcosis is a fatal fungal pneumonia in acquired immunodeficiency syndrome patients. In some cases, the pathogen Cryptococcus neoformans also develops dormant nodules in immunocompetent individuals. In the present study, we demonstrated that fine particulate matter (PM2.5) increased CD146 expression in alveolar epithelial cells and promoted C. neoformans pulmonary infection. Aryl hydrocarbon receptor (AhR) signaling was required for increased expression of CD146 in epithelial cells treated with PM2.5. In a murine model of pulmonary infection, PM2.5 promoted fungal infection, and CD146 deficiency decreased the fugal burden of C. neoformans. Our study may highlight the importance of air pollution to lung mycosis and CD146 as a target for preventing infectious lung diseases. [ABSTRACT FROM AUTHOR]

Objective: Decidual macrophages (dMΦs) have been implicated in fetal tolerance, but little information is known regarding their differentiation capacity and interactions with T cells. The present study aimed to investigate the immunological characteristics of dMΦs at mid and term pregnancy.Methods: The dMΦs were analyzed for their phenotypes and cytokine production by flow cytometry and ELISA, respectively. The transendothelial trafficking model was implemented to allow the dMΦs to differentiate. The differentiated cells from dMΦs were also measured for their phenotypes and cytokine production with same methods. The capacity of dMΦs or the differentiated cells from dMΦs to stimulate allogeneic T lymphocyte proliferation was evaluated by T lymphocyte stimulation assays. T cell differentiation was determined by flow cytometry.Results: The dMΦs in the mid-pregnancy (Mid-dMΦs) resembled the M2 phenotype. The differentiated cells from Mid-dMΦs had little stimulatory capacity on T cell proliferation and favored regulatory T cell differentiation. The dMΦs at term differentiated into dendritic (DC)-like cells, stimulating T cell activation, proliferation, and differentiation into IFN-γ-producing T cellsdecidualConclusions: The present study suggests that the differences in phenotypes and cytokine production between Mid- and Term-dMΦs relate to their different roles in the homeostasis of the maternal-fetal interface. Mid-dMΦs differentiate into DC-like cells with immunosuppressive properties, playing an important role in maintaining homeostasis required for a successful pregnancy. Term-dMΦs differentiate into DC-like cells with immunostimulatory properties, likely involved in the activation of labor. The different differentiation capacities of dMΦs in the varied pregnancy stages may be due to the placental microenvironment. [ABSTRACT FROM AUTHOR]

Objective. Our previous research showed that TCR+CD4-CD8-double-negative (DN) T cells protect renal epithelial cells from cisplatin-induced acute kidney injury (AKI). Therefore, this study is aimed at investigating the mechanism underlying the effect of DN T cells against Cis-induced AKI. Methods. HK-2 cells cultured alone or with DN T cells were treated with or without Cis. After treatment, the cell viability and death were analyzed by a CCK-8 kit and flow cytometric assay with Annexin V/PI staining, respectively. The expressions of inflammatory factors in HK-2 and DN T cells were analyzed using qPCR. The expression levels of nephrotoxicity-associated biomarkers (KIM, calbindin, and TIMP-1), Bcl-2, and angiotensin AT2 receptor (AT2R) were determined by Western blot and qPCR. Results. The administration of cisplatin significantly decreased the cell viability and AT2R expression, and increased cell death, inflammatory factors, and nephrotoxicity-associated biomarkers of HK-2 cells, while these effects were partly attenuated when cocultured with DN T cells. IL-10 expression was significantly increased in DN T cells after coculture, and cisplatin treatment aggravated this elevation. IL-10 supplementation exhibited a similar effect to coculture, whereas anti-IL-10 antibody reversed the effect of coculture on cisplatin-treated HK-2 cells. Finally, PD123319, an AT2R antagonist, also reversed the effect of IL-10 and coculture on the cell viability, death, and the expression of KIM, calbindin, TIMP-1, and Bcl-2 of cisplatin-treated HK-2 cells. Conclusions. DN T cells protected HK-2 cells from cisplatin-induced injury through IL-10/AT2R axis, which may act as a potential target for the treatment of cisplatin-induced AKI. [ABSTRACT FROM AUTHOR]