Immunohistochemical Study of Airways Fibrous Remodeling in Smoking Mice.

The fibrotic remodeling in chronic obstructive pulmonary disease (COPD) is held responsible for narrowing of small airways and thus for disease progression. Oxidant damage and cell senescence factors are recently involved in airways fibrotic remodeling. Unfortunately, we have no indications on their sequential expression at anatomical sites in which fibrotic remodeling develops in smoking subjects.

Smoking Cessation in Mice Does Not Switch off Persistent Lung Inflammation and Does Not Restore the Expression of HDAC2 and SIRT1.

Once COPD is established, pulmonary lesions can only progress and smoking cessation by itself is not sufficient to switch off persistent lung inflammation. Similarly, in former-smoker mice, neutrophil inflammation persists and lung lesions undergo progressive deterioration. The molecular mechanisms underlying disease progression and the inefficiency of smoking cessation in quenching neutrophilic inflammation were studied in male C57 Bl/6 mice after 6 months of rest from smoking cessation.

Lung ultrasound features and relationships with respiratory mechanics of evolving BPD in preterm rabbits and human neonates.

Evolving bronchopulmonary dysplasia (BPD) is characterized by impaired alveolarization leading to lung aeration inhomogeneities. Hyperoxia-exposed preterm rabbits have been proposed to mimic evolving BPD; therefore, we aimed to verify if this model has the same lung ultrasound and mechanical features of evolving BPD in human neonates. Semiquantitative lung ultrasound and lung mechanics measurement was performed in 25 preterm rabbits (28 days of gestation) and 25 neonates (mean gestational age ≈ 26 wk) with evolving BPD.

Anethole Dithiolethione Increases Glutathione in Kidney by Inhibiting -Glutamyltranspeptidase: Biochemical Interpretation and Pharmacological Consequences.

Aims: Anethole dithiolethione (ADT) is a marketed drug to treat xerostomia. Its mechanism of action is still unknown, but several preclinical studies indicate that it is able to increase intracellular glutathione (GSH) and protect against oxidative stress. Here, we investigated the molecular mechanisms behind these effects.

Alveolar Macrophage Phenotype and Compartmentalization Drive Different Pulmonary Changes in Mouse Strains Exposed to Cigarette Smoke.

COPD can manifest itself with different clinical phenotypes characterized by different disease progression and response to therapy. Although a remarkable number of studies have been carried out, little is known about the mechanisms underlying phenotypes that could guide the development of viable future therapies. Several murine strains mirror some human phenotypes after smoke exposure.

Innate Immunity and Cell Surface Receptors in the Pathogenesis of COPD: Insights from Mouse Smoking Models.

Chronic obstructive pulmonary disease (COPD) is mainly associated with smoking habit. Inflammation is the major initiating process whereby neutrophils and monocytes are attracted into the lung microenvironment by external stimuli present in tobacco leaves and in cigarette smoke, which promote chemotaxis, adhesion, phagocytosis, release of superoxide anions and enzyme granule contents. A minority of smokers develops COPD and different molecular factors, which contribute to the onset of the disease, have been put forward.

Ongoing Lung Inflammation and Disease Progression in Mice after Smoking Cessation: Beneficial Effects of Formyl-Peptide Receptor Blockade.

The most important risk factor for chronic obstructive pulmonary disease (COPD) is cigarette smoking. Until now, smoking cessation (SC) is the only treatment effective in slowing down the progression of the disease. However, in many cases SC may only relieve the airflow obstruction and inflammatory response.

Morphological and Functional Characterization of IL-12Rβ2 Chain on Intestinal Epithelial Cells: Implications for Local and Systemic Immunoregulation.

Interaction between intestinal epithelial cells (IECs) and the underlying immune systems is critical for maintaining intestinal immune homeostasis and mounting appropriate immune responses. We have previously showed that the T helper type 1 (T1) cytokine IL-12 plays a key role in the delicate immunological balance in the gut and the lack of appropriate levels of IL-12 had important consequences for health and disease, particularly with regard to food allergy. Here, we sought to understand the role of IL-12 in the regulation of lymphoepithelial cross talk and how this interaction affects immune responses locally and systemically.

Proteinase activated receptor-2 counterbalances the vascular effects of endothelin-1 in fibrotic tight-skin mice.

Background And Purpose: The majority of the severe vascular complications in fibrosis are a consequence of a deregulated activity of mediators controlling vasomotor tone. One of the most important of these mediators is endothelin-1 (ET-1). Here, we have investigated the role of proteinase-activated receptor 2 (PAR2) in the vascular dysfunction in a model of fibrosis, using tight-skin (Tsk) mice.

Severe Reduction in Number and Function of Peripheral T Cells Does Not Afford Protection toward Emphysema and Bronchial Remodeling Induced in Mice by Cigarette Smoke.

The protein Lck (p56(Lck)) is a Src family tyrosine kinase expressed at all stages of thymocyte development and is required for maturation of T cells. The targeted disruption of Lck gene in mice results in severe block in thymocyte maturation with substantial reduction in the development of CD4(+)CD8(+) thymocytes, severe reduction of peripheral T cells, and disruption of T-cell receptor signaling with defective function of T-cell responses. To investigate the role of T lymphocyte in the development of cigarette smoke-induced pulmonary changes, Lck(-/-) mice and corresponding congenic wild-type mice were chronically exposed to cigarette smoke, and their lungs were analyzed by biochemical, immunologic, and morphometric methods.

Ajulemic acid exerts potent anti-fibrotic effect during the fibrogenic phase of bleomycin lung.

Background: Ajulemic acid (AjA) is a synthetic analogue of tetrahydrocannabinol that can prevent and limit progression of skin fibrosis in experimental systemic sclerosis. In this study we investigated whether AjA also prevents and modulates lung fibrosis induced by bleomycin (BLM) when administered in mice during the inflammatory or the fibrogenic phase of the model.

Methods: The anti-inflammatory and antifibrotic efficacy of AjA was evaluated in DBA/2 mice treated orally once a day starting either at day 0 (preventive treatment) or at day 8 (therapeutic treatment) after a single intratracheal instillation of BLM.

Histopathological data of iron and calcium in the mouse lung after asbestos exposure.

This data article contains data related to the research article entitled, "Synchrotron X-ray microscopy reveals early calcium and iron interaction with crocidolite fibers in the lung of exposed mice" [1]. Asbestos fibers disrupt iron homeostasis in the human and mouse lung, leading to the deposition of iron (Fe) onto longer asbestos fibers which forms asbestos bodies (AB) [2]. Similar to Fe, calcium (Ca) is also deposited in the coats of the AB.

Synchrotron X-ray microscopy reveals early calcium and iron interaction with crocidolite fibers in the lung of exposed mice.

Human exposure to asbestos can cause a wide variety of lung diseases that are still a current major health concern, even if asbestos has been banned in many countries. It has been shown in many studies that asbestos fibers, ingested by alveolar macrophages, disrupt lung iron homeostasis by sequestering iron. Calcium can also be deposited on the fibers.

NTPDase1/CD39 and aberrant purinergic signalling in the pathogenesis of COPD.

Purinergic receptor activation via extracellular ATP is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Nucleoside triphosphate diphosphohydrolase-1/CD39 hydrolyses extracellular ATP and modulates P2 receptor signalling.We aimed to investigate the expression and function of CD39 in the pathogenesis of cigarette smoke-induced lung inflammation in patients and preclinical mouse models.

Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1.

Antitumor immunity driven by intratumoral dendritic cells contributes to the efficacy of anthracycline-based chemotherapy in cancer. We identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast and colorectal cancer patients receiving adjuvant chemotherapy. The therapeutic effects of anthracyclines were abrogated in tumor-bearing Fpr1(-/-) mice due to impaired antitumor immunity.

Smoking p66Shc knocked out mice develop respiratory bronchiolitis with fibrosis but not emphysema.

The adaptor protein p66Shc regulates intracellular oxidant levels through the modulation of a forkhead-related transcription factor (FOXO3a). The genetic ablation of p66Shc (p66Shc-/-) renders mice resistant to oxidative stress and p53-dependent apoptosis. We investigated whether p66Shc ablation in mice modifies lung cellular and molecular responses to cigarette smoke (CS) exposure.

The HIV matrix protein p17 promotes the activation of human hepatic stellate cells through interactions with CXCR2 and Syndecan-2.

Background: The human immunodeficiency virus type 1 (HIV-1) p17 is a matrix protein involved in virus life's cycle. CXCR2 and Syndecan-2, the two major coreceptors for the p17 protein, are expressed in hepatic stellate cells (HSCs), a key cell type involved in matrix deposition in liver fibrotic disorders.

Aim: In this report we have investigated the in vitro impact of p17 on HSCs transdifferentiation and function and underlying signaling pathways involved in these processes.

Skeletal muscle oxidative metabolism in an animal model of pulmonary emphysema: formoterol and skeletal muscle dysfunction.

Skeletal muscle dysfunction is a significant contributor to exercise limitation in pulmonary emphysema. This study investigated skeletal muscle oxidative metabolism before and after aerosol exposure to a long-acting β-agonist (LABA), such as formoterol, in the pallid mouse (B6.Cg-Pldnpa/J), which has a deficiency in serum α(1)-antitrypsin (α(1)-PI) and develops spontaneous pulmonary emphysema.

Synthetic cannabinoid ajulemic acid exerts potent antifibrotic effects in experimental models of systemic sclerosis.

Background: Cannabinoids modulate fibrogenesis in scleroderma. Ajulemic acid (AjA) is a non-psychoactive synthetic analogue of tetrahydrocannabinol that can bind the peroxisome proliferator-activated receptor-γ (PPAR-γ). Recent evidence suggests a key role for PPAR-γ in fibrogenesis.

Genetic ablation of the fpr1 gene confers protection from smoking-induced lung emphysema in mice.

Cigarette smoke (CS) is the main causative factor of chronic obstructive pulmonary disease (COPD). Current research supports the concept that airway inflammation is central to the development and progression of the disease. Studies have demonstrated that neutrophils are increased in COPD lungs and that neutrophil-associated products correlate with the development and severity of COPD.

The cannabinoid WIN55, 212-2 abrogates dermal fibrosis in scleroderma bleomycin model.

Objectives: There is increasing evidence that the endocannabinoid system may be involved in pathological fibrosis, and that its modulation might limit fibrotic responses. The aim of this study was to examine the capacity of a synthetic cannabinoid receptor agonist to modify skin fibrosis in the bleomycin mouse model of scleroderma.

Methods: Skin fibrosis was induced by local injections of bleomycin in two groups of DBA/2J mice.

Pulmonary hypertension in smoking mice over-expressing protease-activated receptor-2.

The mechanism(s) involved in the development of pulmonary hypertension (PH) in COPD is still the object of investigation. Cigarette smoke (CS) may lead to remodelling of intrapulmonary vessels and dynamic changes in vascular function, at least in some smokers. A role for proteases in PH has been recently put forward.