Epithelium-derived IL17A Promotes Cigarette Smoke-induced Inflammation and Mucus Hyperproduction.

The airway epithelium is a central modulator of innate and adaptive immunity in the lung. IL17A expression was found to be increased in the airway epithelium; however, the role of epithelium-derived IL17A in chronic obstructive pulmonary disease (COPD) remains unclear. In this study, we aimed to determine whether epithelium-derived IL17A regulates inflammation and mucus hyperproduction in COPD by using a cultured human bronchial epithelial (HBE) cell line in vitro and an airway epithelium IL17A-specific knockout mouse in vivo. Increased IL17A expression was observed in the mouse airway epithelium upon cigarette smoke (CS) exposure or in a mouse model of COPD that was induced by using CS and Eln (elastin). CS extract (CSE) also triggered IL17A expression in HBE cells. Blocking IL17A or IL17RA (IL17 receptor A) effectively attenuated CSE-induced MUC5AC and the inflammatory cytokines IL6, TNF-α, and IL1ß in HBE cells, suggesting that IL17A mediates CSE-induced inflammation and mucin production in an autocrine manner. CSE activated p-JUN (phospho-JUN) and p-JNK (phospho-c-Jun N-terminal kinase), which were also reduced by IL17RA siRNA, and JUN siRNA attenuated CSE-induced IL6 and MUC5AC. In vivo, selective knockout of IL17A in the airway epithelium markedly reduced the neutrophilic infiltration in BAL fluid, peribronchial inflammation, proinflammatory mediators (CXCL1 [CXC ligand 1] and CXCL2), and mucus production in a COPD mouse model. We showed a novel function of airway epithelium-derived IL17A, which can act locally in an autocrine manner to amplify inflammation and increase mucus production in COPD pathogenesis.

Induction of ferroptosis-like cell death of eosinophils exerts synergistic effects with glucocorticoids in allergic airway inflammation.

INTRODUCTION: Eosinophils are critical in allergic disorders, and promoting eosinophil death effectively attenuates allergic airway inflammation. Ferroptosis is a recently described novel form of cell death; however, little is known about ferroptosis in eosinophils and related diseases. This study aimed to investigate the effects of ferroptosis-inducing agents (FINs) on eosinophil death and allergic airway inflammation, and to explore their potential synergistic effect with glucocorticoids (GCs). METHODS: Eosinophils isolated from the peripheral blood of humans or mice were incubated with FINs, and eosinophil ferroptosis was assessed. The in vivo effects of FINs alone or in combination with dexamethasone (DXMS) were examined in a mouse model of allergic airway inflammation. Bronchoalveolar lavage fluid and lung tissue were collected to examine airway inflammation. RESULTS: Treatment with FINs time and dose dependency induced cell death in human and mouse eosinophils. Interestingly, FINs induced non-canonical ferroptosis in eosinophils, which generated morphological characteristics unique to ferroptosis and was iron dependent but was independent of lipid peroxidation. The antioxidants glutathione and N-acetylcysteine significantly attenuated FIN-induced cell death. Treatment with FINs triggered eosinophil death in vivo and eventually relieved eosinophilic airway inflammation in mice. Furthermore, FINs exerted a synergistic effect with DXMS to induce eosinophil death in vitro and to alleviate allergic airway inflammation in vivo. CONCLUSIONS: FINs induced ferroptosis-like cell death of eosinophils, suggesting their use as a promising therapeutic strategy for eosinophilic airway inflammation, especially due to the advantage of their synergy with GCs in the treatment of allergic disorders.

Homeostatic and early-recruited CD101- eosinophils suppress endotoxin-induced acute lung injury.

INTRODUCTION: Acute lung injury (ALI) is a fatal but undertreated condition with severe neutrophilic inflammation, although little is known about the functions of eosinophils in the pathogenesis of ALI. Our objectives were to investigate the roles and molecular mechanisms of eosinophils in ALI. METHODS: Pulmonary eosinophils were identified by flow cytometry. Mice with abundant or deficient eosinophils were used. Cellularity of eosinophils and neutrophils in bronchoalveolar lavage fluid, inflammatory assessment, and survival rate were determined. Human samples were also used for validating experimental results. RESULTS: Blood eosinophils were increased in surviving patients with acute respiratory distress syndrome (ARDS) independent of corticosteroid usage. There existed homeostatic eosinophils in lung parenchyma in mice and these homeostatic eosinophils, originating from the bone marrow, were predominantly CD101-. More CD101- eosinophils could be recruited earlier than lipopolysaccharide (LPS)-initiated neutrophilic inflammation. Loss of eosinophils augmented LPS-induced pulmonary injury. Homeostatic CD101- eosinophils ameliorated, while allergic CD101+ eosinophils exacerbated, the neutrophilic inflammation induced by LPS. Likewise, CD101 expression in eosinophils from ARDS patients did not differ from healthy subjects. Mechanistically, CD101- eosinophils exhibited higher levels of Alox15 and Protectin D1. Administration of Protectin D1 isomer attenuated the neutrophilic inflammation. CONCLUSIONS: Collectively, our findings identify an uncovered function of native CD101- eosinophils in suppressing neutrophilic lung inflammation and suggest a potential therapeutic target for ALI.

Fabrication of polyimide/graphene nanosheet composite fibers via microwave-assisted imidization strategy.

Here, a rapid and efficient strategy was introduced to prepare polyimide/graphene nanosheet (PI/GN) composite fibers by microwave-assisted imidization. The mechanical properties of the PI/GNs (1 wt%) fibers treated by microwave-assisted imidization were apparently improved with the tensile strength of 1.12 GPa at 350 °C, which was approximately 1.7 times as much as those treated with traditional thermal imidization. The PI/GNs (1 wt%) fibers heated by the microwave-assisted imidization method exhibited excellent thermal stabilities of up to 570.3 °C in nitrogen for a 5% weight loss, and a glass transition temperature above 339 °C. The results of the infrared spectrum and thermal properties indicated that the microwave-assisted treatment could promote the imidization degree of the PI/GN fibers prominently. Meanwhile, as a microwave absorber, graphene nanosheets (GNs) could also promote the imidization process by converting microwave energy into thermal energy. The microwave-polyimide/graphene nanosheet (MW-PI/GN) fibers possessed an optimum tensile strength of 1.38 GPa and modulus of 56.82 GPa at the GN content of 0.25 wt%. The 5% weight loss temperature in nitrogen ranged from 520.9 °C to 570.3 °C, and the glass transition temperature was increased from 305.7 °C to 339.1 °C with increasing the GN content.

Preparation of polyimide films via microwave-assisted thermal imidization.

A series of polyimide (PI) films based on aromatic heterocyclic monomers of 3,3',4,4'-biphenyltetracarboxylic dianhydride (BPDA), p-phenylenediamine (p-PDA) and 4,4'-oxydianiline (ODA) were prepared via a microwave-assisted thermal imidization and conventional thermal imidization method at different temperatures. The effects of microwave irradiation on the imidization degree, microstructures, mechanical and thermal properties of PI films were investigated. The imidization degree of the PI films treated with microwave-assisted heating reached a relatively high value at 250 °C, which was twice as much as those treated with traditional thermal imidization. The tensile strength and modulus of PI films treated with microwave-assisted imidization at 300 °C were 187.61 MPa and 2.71 GPa respectively, which were 30% higher than those of PI films treated with thermal imidization. Moreover, the order degree of polymer chains was improved by the microwave-assisted imidization method. The PI films prepared by the microwave-assisted imidization method showed excellent thermal stability with a 5% weight loss temperature of 573 °C under N2. The microwave-assisted thermal imidization proved to be a rapid and efficient way to prepare high-performance polyimide materials.

Hematological indices as simple, inexpensive and practical severity markers of obstructive sleep apnea syndrome: a meta-analysis.

BACKGROUND: Clinical detection of inflammatory markers is useful to assess the degree of nocturnal hypoxia and predict the presence of complications in obstructive sleep apnea syndrome (OSAS) patients. Nowadays, some researchers proposed that hematological parameters could be substituted for novel disease-specific biochemical markers (such as C-reactive protein) because they were comparatively cheap, simple and practical. But there was a contradiction whether the hematological parameters were positively correlated with the OSAS severity. METHODS: Medical databases were searched included PubMed, Web of Science, Scopus, Cochrane Library, Clinical Trial, Embase and Google Scholar (up to March 29, 2018). We used weighted mean differences (WMDs) with 95% confidence intervals (CIs) from random-effects model. RESULTS: Seventeen studies were included in this meta-analysis and results were presented by different hematological parameters. Pooled analysis showed that OSAS was associated with a high level of WBC (white blood cell, 11 studies, 2,206 subjects, WMD: 0.58; 95% CI: 0.31 to 0.85; P<0.0001), NLR (neutrophil-to-lymphocyte ratio, 5 studies, 1416 subjects, WMD: 0.46; 95% CI: 0.13 to 0.80; P=0.007), MPV (mean platelet volume, 8 studies, 1,854 subjects, WMD: 0.63; 95% CI: 0.29 to 0.98; P=0.0004), PDW (platelet distribution width, 6 studies, 1,911 subjects, WMD: 0.76; 95% CI: 0.47 to 1.06; P<0.00001), PLR (platelet-to-lymphocyte ratio, 3 studies, 998 subjects, WMD: 21.76; 95% CI: 8.54 to 34.99; P=0.001), RDW (red cell distribution width, 5 studies, 1,701 subjects, WMD: 0.31; 95% CI: 0.11 to 0.51; P=0.002) and HCT (hematocrit, 3 studies, 662 subjects, WMD: 1.58; 95% CI: 0.52 to 2.64; P=0.003). But OSAS was associated with a low level of LYM (lymphocyte, 5 studies, 1,285 subjects, WMD: -0.27; 95% CI: -0.49 to -0.06; P=0.01). There was a gradual rising trend from mild OSAS to severe OSAS existed in all subgroups. CONCLUSIONS: Hematological indices are comparatively Simple, Inexpensive and Practical Severity Markers of OSAS including WBC, LYM, NLR, MPV, PDW, PLR, RDW and HCT.

mTOR complexes differentially orchestrates eosinophil development in allergy.

Eosinophil infiltration is considered a hallmark in allergic airway inflammation, and the blockade of eosinophil differentiation may be an effective approach for treating eosinophil-related disorders. Mammalian target of rapamycin (mTOR) is a vital modulator in cell growth control and related diseases, and we have recently demonstrated that rapamycin can suppress eosinophil differentiation in allergic airway inflammation. Considering its critical role in haematopoiesis, we further investigated the role of mTOR in eosinophil differentiation in the context of asthmatic pathogenesis. Intriguingly, the inhibition of mTOR, either by genetic deletion or by another pharmacological inhibitor torin-1, accelerated the eosinophil development in the presence of IL-5. However, this was not observed to have any considerable effect on eosinophil apoptosis. The effect of mTOR in eosinophil differentiation was mediated by Erk signalling. Moreover, myeloid specific knockout of mTOR or Rheb further augmented allergic airway inflammation in mice after allergen exposure. Ablation of mTOR in myeloid cells also resulted in an increased number of eosinophil lineage-committed progenitors (Eops) in allergic mice. Collectively, our data uncovered the differential effects of mTOR in the regulation of eosinophil development, likely due to the distinct functions of mTOR complex 1 or 2, which thus exerts a pivotal implication in eosinophil-associated diseases.