ORCID Profile
0000-0003-1826-5018
Current Organisation
Università degli Studi di Torino
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Publisher: Wiley
Date: 08-2004
Publisher: Informa UK Limited
Date: 08-2019
DOI: 10.2147/COPD.S207203
Publisher: Springer Science and Business Media LLC
Date: 05-1998
Abstract: To determine which types of kinin receptor are present in human bronchial epithelial cells we studied the capability of bradykinin to mobilize intracellular Ca2+ ([Ca2+]i) in a human bronchial epithelial cell line (16HBE cells). Human bronchial epithelial cell line transformed with an original defective simian virus 40 (SV40). Bradykinin (0.1 pM to 0.1 microM), des-Arg9 bradykinin (1 microM), des-Arg10) kallidin (1 microM), indomethacin (1 microM), phosphoramidon (1 microM), captopril (1 microM), des-Arg9-[Leu8]bradykinin (1 microM), HOE 140 (DArg-[Hyp3, Thi5, DTic , Oic8]-bradykinin) (1 microM), and NPC 16731 (DArg-[Hyp3, Thi5, DTic7, Tic8]-bradykinin) (1 microM). The mobilization of [Ca2+]i was determined by the fura-2 method. Two s le Wilcoxon rank-sum (Mann-Whitney) test was used for statistical calculations. Bradykinin, but not the selective agonists for kinin B1 receptor des-Arg9 bradykinin and des-Arg10 kallidin, increased the mobilization of [Ca2+]i (EC50, 0.079+/-0.009nM) in 16HBE cells in a concentration-dependent manner. Pretreatment with the cyclooxygenase inhibitor indomethacin (1 microM) or the peptidase inhibitors, phosphoramidon (1 microM) or captopril (1 microM), did not affect the response to bradykinin. The kinin B1 receptor antagonist, des-Arg9-[Leu8]bradykinin (1 microM), was inactive. HOE 140 and NPC 16731, two selective antagonists of the kinin B2 receptor abolished the response to bradykinin (IC50 of HOE 140 and NPC 16731 were 0.52+/-0.037nM and 1.67 +/- 0.41 nM, respectively). The present data indicate the presence of kinin B2 receptors in the 16HBE cells.
Publisher: MDPI AG
Date: 10-06-2020
DOI: 10.3390/JCM9061807
Abstract: Background: Little is known about the innate immune response to viral infections in stable Chronic Obstructive Pulmonary Disease (COPD). Objectives: To evaluate the innate immune mediators related to respiratory viruses in the bronchial biopsies and lung parenchyma of stable COPD patients. Methods: We evaluated the immunohistochemical (IHC) expression of Toll-like receptors 3-7-8-9 (TLR-3-7-8-9), TIR domain-containing adaptor inducing IFNβ (TRIF), Interferon regulatory factor 3 (IRF3), Phospho interferon regulatory factor 3 ( pIRF3), Interferon regulatory factor 7 (IRF7), Phospho interferon regulatory factor 7 (pIRF7), retinoic acid-inducible gene I (RIG1), melanoma differentiation-associated protein 5 (MDA5), Probable ATP-dependent RNA helicase DHX58 ( LGP2), Mitochondrial antiviral-signaling protein (MAVS), Stimulator of interferon genes (STING), DNA-dependent activator of IFN regulatory factors (DAI), forkhead box protein A3(FOXA3), Interferon alfa (IFNα), and Interferon beta (IFNβ) in the bronchial mucosa of patients with mild/moderate (n = 16), severe/very severe (n = 18) stable COPD, control smokers (CS) (n = 12), and control non-smokers (CNS) (n = 12). We performed similar IHC analyses in peripheral lung from COPD (n = 12) and CS (n = 12). IFNα and IFNβ were assessed in bronchoalveolar lavage (BAL) supernatant from CNS (n = 8), CS (n = 9) and mild/moderate COPD (n = 12). Viral load, including adenovirus-B, -C, Bocavirus, Respiratory syncytial Virus (RSV),Human Rhinovirus (HRV), Coronavirus, Influenza virus A (FLU-A), Influenza virus B (FLU-B), and Parainfluenzae-1 were measured in bronchial rings and lung parenchyma of COPD patients and the related control group (CS). Results: Among the viral-related innate immune mediators, RIG1, LGP2, MAVS, STING, and DAI resulted well expressed in the bronchial and lung tissues of COPD patients, although not in a significantly different mode from control groups. Compared to CS, COPD patients showed no significant differences of viral load in bronchial rings and lung parenchyma. Conclusions: Some virus-related molecules are well-expressed in the lung tissue and bronchi of stable COPD patients independently of the disease severity, suggesting a “primed” tissue environment capable of sensing the potential viral infections occurring in these patients.
Publisher: Elsevier BV
Date: 11-2005
DOI: 10.1016/J.JACI.2005.06.034
Abstract: Reactive nitrogen species, formed via the reaction of nitric oxide (NO) with superoxide anion and via (myelo)peroxidase-dependent oxidation of NO(2)(-), have potent proinflammatory and oxidizing actions. Reactive nitrogen species formation and nitrosative stress are potentially involved in chronic obstructive pulmonary disease (COPD) pathogenesis. To investigate the expression of markers of nitrosative stress, including nitrotyrosine (NT), inducible NO synthase (iNOS), endothelial NO synthase (eNOS), myeloperoxidase (MPO), and xanthine oxidase (XO) in bronchial biopsies and bronchoalveolar lavage from patients with mild to severe stable COPD compared with control groups (smokers with normal lung function and nonsmokers). The expression of NT, iNOS, eNOS, MPO and XO in the bronchial mucosa and bronchoalveolar lavage of patients was measured by using immunohistochemistry, Western blotting, and ELISA and correlated with the inflammatory cell profile. Patients with severe COPD in stable phase had higher numbers of NT(+) and MPO(+) cells in their bronchial submucosa compared with mild/moderate COPD, smokers with normal lung function, and nonsmokers (P < .01). iNOS(+) and eNOS(+) but not XO(+) cells were significantly increased in smokers with COPD or normal lung function compared with nonsmokers (P < .05 and P < .01, respectively). In patients with COPD, the number of MPO(+) cells was significantly correlated with the number of neutrophils (r = +0.61 P < .0025) in the bronchial submucosa. Furthermore, the number of NT(+) and MPO(+) cells was negatively correlated with postbronchodilator FEV(1). These data suggest that nitrosative stress, mainly mediated by MPO and neutrophilic inflammation, may contribute to the pathogenesis of severe COPD.
Publisher: Elsevier BV
Date: 04-2018
Publisher: Public Library of Science (PLoS)
Date: 28-08-2015
Publisher: S. Karger AG
Date: 2015
DOI: 10.1159/000375168
Abstract: b i Background: /i /b The role of mitogen-activated protein kinases (MAPK) in regulating the inflammatory response in the airways of patients with chronic obstructive pulmonary disease (COPD) and asthmatic patients is unclear. b i Objectives: /i /b To investigate the expression of activated MAPK in lungs of COPD patients and in bronchial biopsies of asthmatic patients and to study MAPK expression in bronchial epithelial cells in response to oxidative and inflammatory stimuli. b i Methods: /i /b Immunohistochemical expression of phospho (p)-p38 MAPK, p-JNK1 and p-ERK1/2 was measured in bronchial mucosa in patients with mild/moderate (n = 17), severe/very severe (n = 16) stable COPD, control smokers (n = 16), control non-smokers (n = 9), in mild asthma (n = 9) and in peripheral airways from COPD patients (n = 15) and control smokers (n = 15). Interleukin (IL)-8 and MAPK mRNA was measured in stimulated 16HBE cells. b i Results: /i /b No significant differences in p-p38 MAPK, p-JNK or p-ERK1/2 expression were seen in bronchial biopsies and peripheral airways between COPD and control subjects. Asthmatics showed increased submucosal p-p38 MAPK expression compared to COPD patients (p 0.003) and control non-smokers (p 0.05). Hydrogen peroxide (H sub /sub O sub /sub ), cytomix (tumour necrosis factor-α + IL-1β + interferon-& #947 ) and lipopolysaccharide (LPS) upregulated IL-8 mRNA at 1 or 2 h. p38 MAPKα mRNA was significantly increased after H sub /sub O sub /sub and LPS treatment. JNK1 and ERK1 mRNA were unchanged after H sub /sub O sub /sub , cytomix or LPS treatments. b i Conclusion: /i /b p-p38 MAPK expression is similar in stable COPD and control subjects but increased in the bronchi of mild asthmatics compared to stable COPD patients. p38 MAPK mRNA is increased after bronchial epithelial challenges in vitro. These data together suggest a potential role for this MAPK in Th2 inflammation and possibly during COPD exacerbations.
Publisher: European Respiratory Society (ERS)
Date: 07-2004
DOI: 10.1183/09031936.04.00080303
Abstract: Activation of the transcription factor signal transducer and activator of transcription (STAT)-4 is critical for the differentiation of T-helper 1 cells/type-1 cytotoxic T-cells and the production of interferon (IFN)-gamma. Expression of STAT4, phospho-STAT4, IFN-gamma and T-box expressed in T-cells (T-bet) proteins in bronchial biopsies and bronchoalveolar lavage (BAL)-derived lymphocytes, obtained from 12 smokers with mild/moderate chronic obstructive pulmonary disease (COPD) (forced expiratory volume in one second (FEV1) 59 +/- 16% predicted), 14 smokers with normal lung function (FEV1 106 +/- 12% pred) and 12 nonsmoking subjects (FEV1 111 +/- 14% pred), was examined by immunohistochemistry and immunocytochemistry. In bronchial biopsies of COPD patients, the number of submucosal phospho-STAT4+ cells was increased (240 (22-406) versus 125 (0-492) versus 29 (0-511) cells mm(-2)) when compared with both healthy smokers and control nonsmokers, respectively. In smokers, phospho-STAT4+ cells correlated with the degree of airflow obstruction and the number of IFN-gamma+ cells. Similar results were seen in BAL (2.8 (0.2-5.9) versus 1.03 (0.09-1.6) versus 0.69 (0-2.3) lymphocytes x mL(-1) x 10(3)). In all smokers who underwent lavage, phospho-STAT4+ lymphocytes correlated with airflow obstruction and the number of IFNgamma+ lymphocytes. T-bet expression was not altered in bronchial biopsies and BAL-derived lymphocytes between the three groups. In conclusion, this study suggests that stable mild/moderate chronic obstructive pulmonary disease is associated with an active T-helper 1 cell/type-1 cytotoxic T-cell inflammatory process involving activation of signal transducer and activator of transcription 4 and interferon-gamma production.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 24-11-2021
DOI: 10.1126/SCITRANSLMED.AAV7223
Abstract: Inhibition of cigarette smoke–induced microRNA-21 suppresses chronic obstructive pulmonary disease through effects on a SATB1/S100A9/NF-κB axis.
Publisher: European Respiratory Society (ERS)
Date: 05-2017
DOI: 10.1183/13993003.02006-2016
Abstract: Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD. Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial mucosa of subjects with stable COPD of different severity (n=34), control smokers (n=12) and nonsmokers (n=12). The bronchial bacterial load of Pseudomonas aeruginosa , Haemophilus influenzae , Moraxella catarrhalis and Streptococcus pneumoniae was measured by quantitative real-time PCR. TLR4 and NOD1 expression was increased in the bronchial mucosa of patients with severe/very severe stable COPD compared with control subjects. TLR4 bronchial epithelial expression correlated positively with CD4 + and CD8 + cells and airflow obstruction. NOD1 expression correlated with CD8 + cells. The bronchial load of P. aeruginosa was directly correlated, but H. influenzae inversely correlated, with the degree of airflow obstruction. Bacterial load did not correlate with inflammatory cells. Bronchial epithelial overexpression of TLR4 and NOD1 in severe/very severe stable COPD, associated with increased bronchial inflammation and P. aeruginosa bacterial load, may play a role in the pathogenesis of COPD.
No related grants have been discovered for Fabio Luigi Massimo Ricciardolo.