Publications by authors named "Sonja Rust"

7 Publications

  • Page 1 of 1

Role of Cigarette Smoke on Angiotensin-Converting Enzyme-2 Protein Membrane Expression in Bronchial Epithelial Cells Using an Air-Liquid Interface Model.

Front Pharmacol 2021 30;12:652102. Epub 2021 Mar 30.

Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.

Prevalence studies of current smoking, among hospitalized COVID-19 patients, demonstrated an unexpectedly low prevalence among patients with COVID-19. The aim of the present study was to evaluate the effect of smoke from cigarettes on ACE-2 in bronchial epithelial cells. Normal bronchial epithelial cells (H292) were exposed to smoke by an air-liquid-interface (ALI) system and ACE-2 membrane protein expression was evaluated after 24 h from exposure. Our transcriptomics data analysis showed a significant selective reduction of membrane ACE-2 expression (about 25%) following smoking exposure. Interestingly, we observed a positive direct correlation between ACE-2 reduction and nicotine delivery. Furthermore, by stratifying GSE52237 as a function of ACE-2 gene expression levels, we highlighted 1,012 genes related to ACE-2 in smokers and 855 in non-smokers. Furthermore, we showed that 161 genes involved in the endocytosis process were highlighted using the online pathway tool KEGG. Finally, 11 genes were in common between the ACE-2 pathway in smokers and the genes regulated during endocytosis, while 12 genes with non-smokers. Interestingly, six in non-smokers and four genes in smokers were closely involved during the viral internalization process. Our data may offer a pharmaceutical role of nicotine as potential treatment option in COVID-19.
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http://dx.doi.org/10.3389/fphar.2021.652102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042260PMC
March 2021

Health outcomes in COPD smokers using heated tobacco products: a 3-year follow-up.

Intern Emerg Med 2021 Apr 23;16(3):687-696. Epub 2021 Mar 23.

Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

Given that many patients with chronic obstructive pulmonary disease (COPD) smoke despite their symptoms, it is important to understand the long-term health impact of cigarette substitution with heated tobacco products (HTPs). We monitored health parameters for 3 years in COPD patients who substantially attenuated or ceased cigarette consumption after switching to HTPs. Changes in daily cigarette smoking, annualized disease exacerbations, lung function indices, patient-reported outcomes (CAT scores) and 6-minute walk distance (6MWD) from baseline were measured in COPD patients using HTPs at 12, 24 and 36 months. These were compared to a group of age- and sex-matched COPD patients who continued smoking. Complete data sets were available for 38 patients (19 in each group). Subjects using HTPs had a substantial decrease in annualized COPD exacerbations within the group mean (± SD) from 2.1 (± 0.9) at baseline to 1.4 (± 0.8), 1.2 (± 0.8) and 1.3 (± 0.8) at 12-, 24- and 36-month follow-up (p < 0.05 for all visits). In addition, substantial and clinically significant improvements in CAT scores and 6MWD were identified at all three time points in the HTP cohort. No significant changes were observed in COPD patients who continued smoking. This study is the first to describe the long-term health effects of HTP use in COPD patients. Consistent improvements in respiratory symptoms, exercise tolerance, quality of life, and rate of disease exacerbations were observed in patients with COPD who abstained from smoking or substantially reduced their cigarette consumption by switching to HTP use.
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http://dx.doi.org/10.1007/s11739-021-02674-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049911PMC
April 2021

Nicotine dosimetry and stability in cambridge filter PADs (CFPs) following different smoking regime protocols and storage conditions.

Regul Toxicol Pharmacol 2021 Jun 18;122:104917. Epub 2021 Mar 18.

Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", Via S. Sofia, 87, 95123, Catania, Italy; Center of Excellence for the Acceleration of Harm Reduction (CoEHAR), University of Catania, Via S. Sofia, 97, 95123, Catania, Italy. Electronic address:

Despite the growing numbers of studies on cigarettes and electronic nicotine delivery products (ENDs), no standard assessment of nicotine stability in various matrix post exposure is currently available. The aim of the present study was to evaluate the optimal standard condition to store Cambridge Filter Pads (CFPs) before chemical analysis in order to guarantee the titer of nicotine.We further performed data normalization according to different smoking or vaping runs. Smoke and vapor generated respectively by a reference tobacco cigarette (1R6F) and ENDs under different exposure regimes (ISO, HCI and CRM81) were collected on CFPs as total particulate matter (TPM) and subsequently analyzed for nicotine content. For each exposure, some CFPs were analyzed at time zero, whereas the others were stored under different conditions for nicotine assessment after 30 days. Principal Component Analysis (PCA) showed the best correlation between nicotine on CFPs and TPM for normalization. This study suggests that different exposure regimes and products can affect the preservation of nicotine titer on CFPs while samples storage at -80 °C may prevent the loss of nicotine. Finally, normalization of nicotine with TPM is strongly recommended for regulatory purpose.
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http://dx.doi.org/10.1016/j.yrtph.2021.104917DOI Listing
June 2021

IDO2 is critical for IDO1-mediated T-cell regulation and exerts a non-redundant function in inflammation.

Int Immunol 2014 Jul 8;26(7):357-67. Epub 2014 Jan 8.

Lankenau Institute for Medical Research, Wynnewood, PA 19096, USA Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA Department of Pathology, Anatomy and Cell Biology, Jefferson Medical School, Thomas Jefferson University, Philadelphia, PA 19107, USA

IDO2 is implicated in tryptophan catabolism and immunity but its physiological functions are not well established. Here we report the characterization of mice genetically deficient in IDO2, which develop normally but exhibit defects in IDO-mediated T-cell regulation and inflammatory responses. Construction of this strain was prompted in part by our discovery that IDO2 function is attenuated in macrophages from Ido1 (-/-) mice due to altered message splicing, generating a functional mosaic with implications for interpreting findings in Ido1 (-/-) mice. No apparent defects were observed in Ido2 (-/-) mice in embryonic development or hematopoietic differentiation, with wild-type profiles documented for kynurenine in blood serum and for immune cells in spleen, lymph nodes, peritoneum, thymus and bone marrow of naive mice. In contrast, upon immune stimulation we determined that IDO1-dependent T regulatory cell generation was defective in Ido2 (-/-) mice, supporting Ido1-Ido2 genetic interaction and establishing a functional role for Ido2 in immune modulation. Pathophysiologically, both Ido1 (-/-) and Ido2 (-/-) mice displayed reduced skin contact hypersensitivity responses, but mechanistic distinctions were apparent, with only Ido2 deficiency associated with a suppression of immune regulatory cytokines that included GM-CSF, G-CSF, IFN-γ, TNF-α, IL-6 and MCP-1/CCL2. Different contributions to inflammation were likewise indicated by the finding that Ido2 (-/-) mice did not phenocopy Ido1 (-/-) mice in the reduced susceptibility of the latter to inflammatory skin cancer. Taken together, our results offer an initial glimpse into immune modulation by IDO2, revealing its genetic interaction with IDO1 and distinguishing its non-redundant contributions to inflammation.
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http://dx.doi.org/10.1093/intimm/dxt073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432394PMC
July 2014

IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan.

Oncoimmunology 2012 Dec;1(9):1460-1468

New Link Genetics Corporation; Ames, IA USA.

Tryptophan catabolism by indoleamine 2,3-dioxygenase (IDO) alters inflammation and favors T-cell tolerance in cancer, but the underlying molecular mechanisms remain poorly understood. The integrated stress response kinase GCN2, a sensor of uncharged tRNA that is activated by amino acid deprivation, is recognized as an important effector of the IDO pathway. However, in a mouse model of inflammatory carcinogenesis, ablation of Gcn2 did not promote resistance against tumor development like the absence of IDO does, implying the existence of additional cancer-relevant pathways that operate downstream of IDO. Addressing this gap in knowledge, we report that the IDO-mediated catabolism of tryptophan also inhibits the immunoregulatory kinases mTOR and PKC-Θ, along with the induction of autophagy. These effects were relieved specifically by tryptophan but also by the experimental agent 1-methyl-D-tryptophan (D-1MT, also known as NLG8189), the latter of which reversed the inhibitory signals generated by IDO with higher potency. Taken together, our results implicate mTOR and PKC-Θ in IDO-mediated immunosuppressive signaling, and they provide timely insights into the unique mechanism of action of D-1MT as compared with traditional biochemical inhibitors of IDO. These findings are important translationally, because they suggest broader clinical uses for D-1MT against cancers that overexpress any tryptophan catabolic enzyme (IDO, IDO2 or TDO). Moreover, they define mTOR and PKC-Θ as candidate pharmacodynamic markers for D-1MT responses in patients recruited to ongoing phase IB/II cancer trials, addressing a current clinical need.
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http://dx.doi.org/10.4161/onci.21716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525601PMC
December 2012

Zinc protoporphyrin IX stimulates tumor immunity by disrupting the immunosuppressive enzyme indoleamine 2,3-dioxygenase.

Mol Cancer Ther 2010 Jun 8;9(6):1864-71. Epub 2010 Jun 8.

New Link Genetics Corporation, Ames, Iowa, USA.

The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase (IDO) has emerged as an important driver of immune escape in a growing number of cancers and cancer-associated chronic infections. In this study, we define novel immunotherapeutic applications for the heme precursor compound zinc protoporphyrin IX (ZnPP) based on our discovery that it is a potent small-molecule inhibitor of IDO. Inhibitory activity was determined using in vitro and in-cell enzyme assays as well as a novel in vivo pharmacodynamic system. An irreversible mechanism of inhibition was documented, consistent with competition for heme binding in newly synthesized cellular protein. siRNA methodology and an IDO-deficient mouse strain were used to verify the specificity of ZnPP as an IDO inhibitor. In a preclinical model of melanoma, ZnPP displayed antitumor properties that relied on T-cell function and IDO integrity. ZnPP also phenocopied the known antitumor properties of IDO inhibitors in preclinical models of skin and breast carcinoma. Our results suggest clinical evaluation of ZnPP as an adjuvant immunochemotherapy in chronic infections and cancers in which there is emerging recognition of a pathophysiologic role for IDO dysregulation.
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http://dx.doi.org/10.1158/1535-7163.MCT-10-0185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885048PMC
June 2010