Chitotriosidase inhibits allergic asthmatic airways via regulation of TGF-β expression and Foxp3+ Treg cells

Abstract

Background

Chitotriosidase (Chitnase 1, Chit1), a major true chitinase in humans, is induced in childhood asthma and has been implicated in the pathogenesis of a variety of inflammatory and tissue remodeling responses. We hypothesized that Chit1 plays a significant role in the pathogenesis of allergic asthma. To identify the role of Chit1, the mechanisms that underlie these contributions and the relevance of these murine findings to childhood asthma.

Methods

Wild type and Chit1-deficient mice and cells in culture were used to define the roles of Chit1 in models of allergic adaptive Th2 inflammation. In addition, the levels of sputum Chit1 were evaluated in pediatric asthma patients and compared to control.

Results

The levels of sputum Chit1 were significantly increased in the patients with childhood asthma. Mice with Chit1 null mutation demonstrated enhanced allergic Th2 inflammatory and cytokine and IgE responses to OVA or house dust mite allergen sensitization and challenge. However, the expression levels of TGF-β1 were significantly decreased with a diminished number of Foxp3⁺ regulatory T cells (Treg) in the lungs of Chit1^-/- mice compared to WT controls. In vitro, the absence of Chit1 significantly reduced TGF-β-stimulated conversion of CD4⁺CD25^- naïve T cells to CD4⁺Foxp3⁺ Treg cells, suggesting Chit1 is required for optimal effect of TGF-β1 in Treg cell differentiation.

Conclusion

Chit1 plays a protective role in the pathogenesis of allergic inflammation and asthmatic airway responses via regulation of TGF-β expression and Foxp3⁺ Treg cells.

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Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases After Treatment: A Follow-Up Study

Thyroid , Vol. 0, No. 0.


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Polymorph formation for a zeolitic imidazolate framework composition - Zn(Im)2

Publication date: 15 July 2018
Source:Microporous and Mesoporous Materials, Volume 265
Author(s): Chao Zhou, Malwina Stepniewska, Jens Martin Sørensen, Luca Scarpa, Giuliana Magnacca, Vittorio Boffa, Thomas D. Bennett, Yuanzheng Yue
We study the effect of synthesis time and temperature on the crystal formation, morphology and size of zeolitic imidazolate frameworks (ZIFs) with the Zn(Im)2 composition by using the solution mixing method. The crystal structure, morphology and thermodynamic properties of the ZIFs were characterized by powder X-ray diffraction, scanning electron microscopy and nitrogen sorption isotherms. Our results indicate that the synthesis time significantly influences the structure and topology of crystal products. The crystal structure transforms from ZIF-coi to the progressively denser polymorphs (ZIF-zec, ZIF-nog and ZIF-zni) upon increasing synthesis time from 18 to 120 hours at 10 °C, in accordance with Ostwald's step rule. Increasing synthesis temperature does not change the formation of the ZIF-zec crystals but affects their morphologies and porosities. Both ZIF-nog and ZIF-zec exhibit relatively large surface areas (>500 m²/g). Furthermore, heating ZIF-nog and ZIF-zec causes recrystallization to ZIF-zni and subsequent melting. Quenching the MOF-liquid results in Zn(Im)2 glass. This work helps to understand and control the crystal formation of ZIFs, and reveals two new MOF glass formers.



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Penaeus vannamei protease stabilizing process of ZnS nanoparticles

Publication date: June 2018
Source:International Journal of Biological Macromolecules, Volume 112
Author(s): Mozhgan Razzaghi, Ahmad Homaei, Elaheh Mosaddegh
The protease enzyme purified from the Penaeus vannamei shrimp has unique properties, so improving the stability of this enzyme can improve their practical applications. In this study, ZnS nanoparticles, which have special properties for enzyme immobilization, were synthesized using a chemical precipitation method, and Penaeus vannamei protease was successfully immobilized on them. The size, structure, and morphology of the ZnS nanoparticles, and the immobilization of the protease were studied, using Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FT-IR) spectroscopy, UV–Vis spectroscopy and Dynamic Light Scattering (DLS) analysis. We show that the immobilized enzyme has improved functionality at high temperatures, extreme pH conditions (pH3 and 12), and during storage. Immobilization increased the optimum temperature range of the enzyme, but did not change the pH optimum, which remained at pH7. Immobilization of P. vannamei protease enzyme increased the Km and decreased kcat/Km. These results indicate that P. vannamei protease immobilized on ZnS nanoparticles, has improved properties due to its high stability and unique properties, can be used for biotechnology applications.



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Preparation, Purification, and Identification of a Monoclonal Antibody Against the C-Terminal Domain of Semaphorin3F

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy , Vol. 0, No. 0.


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Onabotulinum Toxin A in Adductor Spasmodic Dysphonia and Laryngeal Tremor

This cohort study examines the outcomes of onabotulinum toxin A treatment in patients with adductor spasmodic dysphonia with or without lateral laryngeal tremor.

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Medical Student Knowledge of Human Papillomavirus–Positive Head and Neck Cancer

This survey examines knowledge of the association of human papillomavirus and head and neck cancer among students at 10 New York State medical schools.

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