Annexin-A1 (ANXA1) is a glucocorticoid-induced protein with multiple actions in the regulation of inflammatory cell activation. The anti-inflammatory protein ANXA1 and its N-formyl peptide receptor 2 (FPR2) have protective effects on organ fibrosis. However, the exact role of ANXA1 in asthma remains to be determined. The aim of this study was to identify the role of ANXA1 in bronchial asthma. In mice sensitized and challenged with ovalbumin (OVA-OVA mice) and mice sensitized with saline and challenged with air (control mice), we investigated the potential links between ANXA1 levels and bronchial asthma using ELISA, immunoblotting, and immunohistochemical staining. Moreover, we also determined ANXA1 levels in blood from 50 asthmatic patients (stable and exacerbated states). ANXA1 protein levels in lung tissue and bronchoalveolar lavage fluid were significantly higher in OVA-OVA mice compared with control mice. FPR2 protein levels in lung tissue were significantly higher in OVA-OVA mice compared with control mice. Plasma ANXA1 levels were increased in asthmatic patients compared with healthy controls. Plasma ANXA1 levels were significantly lower in exacerbated patients compared with stable patients with bronchial asthma (p < 0.05). The plasma ANXA1 levels in controlled asthmatic patients were correlated with forced expiratory volume in 1 s (FEV1) (r = − 0.191, p = 0.033) and FEV1/forced vital capacity (FVC) (r = −0.202, p = 0.024). These results suggest that ANXA1 may be a potential marker and therapeutic target for asthma.

Particle inhalation–induced lung inflammation acts as an adjuvant to allergens or respiratory viral infection in a process that is mediated by macrophages and epitheliums. The production of interleukin (IL)-4 and IL-13 by activated T cells is involved in the augmentation of Th2-type immune responses to particles, and IL-25 induces the synthesis of IL-4 and IL-13. However, whether IL-13 and IL-25 are directly regulated by particle instillation in the lung has not been studied. The aim of this study was to reveal particle induction of IL-13 and IL-25 in the lung. TiO2 instillation potently induced the mRNA expression for IL-25 and IL-13 in lung tissue extracts 24 h after treatment, as compared with the sham group. Immunostaining for IL-25 and IL-13 showed strong positivity for macrophages in the inflammatory lung lesions of TiO2-treated rats. The alveolar macrophages expressed IL-25 and IL-13 24 h after in vitro stimulation with TiO2 particles in dose- and time-dependent manners, with maximal induction at 24 and 48 h after stimulation, respectively. The sequence of the rat IL-25 gene is 95% homologous with the mouse IL-25 gene. These findings indicate that alveolar macrophages play an important role in particle-induced lung inflammation via direct induction of IL-13 and IL-25 production.

No effective treatment for acute lung injury and fibrosis currently exists. Aim of this study was to investigate the time-dependent effect of bone marrow-derived mesenchymal stem cells (BMDMSCs) on bleomycin (BLM)-induced acute lung injury and fibrosis and nitric oxide metabolites and inflammatory cytokine production.

Rationale: Idiopathic pulmonary fibrosis (IPF) is caused by alterations in expression of proteins involved in multiple pathways, including matrix deposition, inflammation, injury, and repair. Objectives: To understand the pathogenic changes in lung protein expression in IPF and to evaluate apolipoprotein (Apo) A-I as a candidate therapeutic molecule. Methods: Two-dimensional electrophoresis was adopted for differential display proteomics. Reverse-transcriptase polymerase chain reaction, Western blotting, immunohistochemical staining, and ELISA were performed for identification and quantitative measurement of Apo A-I in bronchoalveolar lavage fluids from subjects with IPF and experimental bleomycin-induced mice. Measurements and Main Results: Sixteen protein spots showed differences in relative intensity between IPF (n = 14) and healthy control subjects (n = 8). Nano liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed increase of haptoglobulin and decrease of α₁-antitrypsin, α₁-antichymotrypsin, macrophage capping protein, angiotensinogen, hemoglobin chain B, Apo A-I, clusterin, protein disulfide isomerase A3, immunoglobulin, and complement C4A in IPF compared with normal control subjects (P = 0.006–0.044). Apo A-I concentrations were lower in bronchoalveolar lavage fluids from subjects with IPF (n = 28) than in normal control subjects (n = 18; P < 0.01). In bleomycin-treated mice, Apo A-I protein in BALF was lower than that in sham-treated control animals. Immunohistochemical analysis showed positive staining on intraalveolar macrophages and epithelial cells of the lungs. Intranasal treatment with Apo A-I protein reduced the bleomycin-induced increases in number of inflammatory cells and collagen deposition in sham-treated mice in a dose-dependent manner. Conclusions: Alterations of several inflammatory and antiinflammatory proteins in the lungs may be related to the pathogenesis of IPF, and local treatment with Apo A-I is very effective against the development of experimental lung injury and fibrosis.