Faculty Opinions recommendation of The IL-33/ST2 axis is crucial in type 2 airway responses induced by Staphylococcus aureus-derived serine protease-like protein D.

In cystic fibrosis (CF) infectious and allergic airway inflammation cause pulmonary exacerbations that destroy the lungs. Staphylococcus aureus is a common long-term colonizer and cause of recurrent airway infections in CF. The pathogen is also associated with respiratory allergy; especially the staphylococcal serine protease-like proteins (Spls) can induce type 2 immune responses in humans and mice. We measured the serum IgE levels specific to 7 proteases of S. aureus by ELISA, targeting 5 Spls (76 CF patients and 46 controls) and the staphopains A and B (16 CF patients and 46 controls). Then we compared cytokine release and phenotype of T cells that had been stimulated with Spls between 5 CF patients and 5 controls. CF patients had strongly increased serum IgE binding to all Spls but not to the staphopains. Compared to healthy controls, their Spl-stimulated T cells released more type 2 cytokines (IL-4, IL-5, IL-13) and more IL-6 with no difference in the secretion of type 1- or type 3 cytokines (IFNγ, IL-17A, IL-17F). IL-10 production was low in CF T cells. The phenotype of the Spl-exposed T cells shifted towards a Th2 or Th17 profile in CF but to a Th1 profile in controls. Sensitization to S. aureus Spls is common in CF. This discovery could explain episodes of allergic inflammation of hitherto unknown causation in CF and extend the diagnostic and therapeutic portfolio.

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Contrasting roles for the receptor for advanced glycation end-products on structural cells in allergic airway inflammation vs. airway hyperresponsiveness

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00087.2015 ◽

2015 ◽

Vol 309 (8) ◽

pp. L789-L800 ◽

Cited By ~ 13

Author(s):

Akihiko Taniguchi ◽

Nobuaki Miyahara ◽

Koichi Waseda ◽

Etsuko Kurimoto ◽

Utako Fujii ◽

...

Keyword(s):

Airway Inflammation ◽

Airway Hyperresponsiveness ◽

Allergic Airway Inflammation ◽

T Helper ◽

Advanced Glycation ◽

Glycation End Products ◽

End Products ◽

Group 2 ◽

Airway Responses

The receptor for advanced glycation end-products (RAGE) is a multiligand receptor that belongs to the immunoglobulin superfamily. RAGE is reported to be involved in various inflammatory disorders; however, studies that address the role of RAGE in allergic airway disease are inconclusive. RAGE-sufficient (RAGE+/+) and RAGE-deficient (RAGE−/−) mice were sensitized to ovalbumin, and airway responses were monitored after ovalbumin challenge. RAGE−/− mice showed reduced eosinophilic inflammation and goblet cell metaplasia, lower T helper type 2 (Th2) cytokine production from spleen and peribronchial lymph node mononuclear cells, and lower numbers of group 2 innate lymphoid cells in the lung compared with RAGE+/+ mice following sensitization and challenge. Experiments using irradiated, chimeric mice showed that the mice expressing RAGE on radio-resistant structural cells but not hematopoietic cells developed allergic airway inflammation; however, the mice expressing RAGE on hematopoietic cells but not structural cells showed reduced airway inflammation. In contrast, absence of RAGE expression on structural cells enhanced innate airway hyperresponsiveness (AHR). In the absence of RAGE, increased interleukin (IL)-33 levels in the lung were detected, and blockade of IL-33 receptor ST2 suppressed innate AHR in RAGE−/− mice. These data identify the importance of RAGE expressed on lung structural cells in the development of allergic airway inflammation, T helper type 2 cell activation, and group 2 innate lymphoid cell accumulation in the airways. RAGE on lung structural cells also regulated innate AHR, likely through the IL-33-ST2 pathway. Thus manipulating RAGE represents a novel therapeutic target in controlling allergic airway responses.

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Allergen-induced airway responses

European Respiratory Journal ◽

10.1183/13993003.00536-2015 ◽

2015 ◽

Vol 46 (3) ◽

pp. 819-831 ◽

Cited By ~ 52

Author(s):

Gail M. Gauvreau ◽

Amani I. El-Gammal ◽

Paul M. O'Byrne

Keyword(s):

Early Response ◽

Myeloid Dendritic Cells ◽

Clinical Model ◽

Allergen Inhalation ◽

Chemotactic Factors ◽

Inhalation Challenge ◽

Airway Responses ◽

Neutral Proteases ◽

Allergen Inhalation Challenge

Environmental allergens are an important cause of asthma and can contribute to loss of asthma control and exacerbations. Allergen inhalation challenge has been a useful clinical model to examine the mechanisms of allergen-induced airway responses and inflammation. Allergen bronchoconstrictor responses are the early response, which reaches a maximum within 30 min and resolves by 1–3 h, and late responses, when bronchoconstriction recurs after 3–4 h and reaches a maximum over 6–12 h. Late responses are followed by an increase in airway hyperresponsiveness. These responses occur when IgE on mast cells is cross-linked by an allergen, causing degranulation and the release of histamine, neutral proteases and chemotactic factors, and the production of newly formed mediators, such as cysteinyl leukotrienes and prostaglandin D2. Allergen-induced airway inflammation consists of an increase in airway eosinophils, basophils and, less consistently, neutrophils. These responses are mediated by the trafficking and activation of myeloid dendritic cells into the airways, probably as a result of the release of epithelial cell-derived thymic stromal lymphopoietin, and the release of pro-inflammatory cytokines from type 2 helper T-cells. Allergen inhalation challenge has also been a widely used model to study potential new therapies for asthma and has an excellent negative predictive value for this purpose.

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Staphylococcus aureus proteoglycans can limit type 2 T cell differentiation: Implications for atopic dermatitis

10.22541/au.158921553.30663436 ◽

2020 ◽

Author(s):

Vladimir Gim nez Rivera ◽

Adam Peres ◽

Gaurav Isola ◽

Denis Sasseville ◽

Robert Bissonnette ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Atopic Dermatitis ◽

Cell Differentiation ◽

T Cell ◽

T Cell Differentiation

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Vaccinomics Approach for Designing Potential Peptide Vaccine by TargetingShigellaspp. Serine Protease Autotransporter Subfamily Protein SigA

Journal of Immunology Research ◽

10.1155/2017/6412353 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 17

Author(s):

Arafat Rahman Oany ◽

Tahmina Pervin ◽

Mamun Mia ◽

Motaher Hossain ◽

Mohammad Shahnaij ◽

...

Keyword(s):

Serine Protease ◽

Bacillary Dysentery ◽

Peptide Vaccine ◽

Human Leukocyte ◽

World Population ◽

Potential Core ◽

Antigenic Protein ◽

Leukocyte Antigen

Shigellosis, a bacillary dysentery, is closely associated with diarrhoea in human and causes infection of 165 million people worldwide per year. Casein-degrading serine protease autotransporter of enterobacteriaceae (SPATE) subfamily protein SigA, an outer membrane protein, exerts both cytopathic and enterotoxic effects especially cytopathic to human epithelial cell type-2 (HEp-2) and is shown to be highly immunogenic. In the present study, we have tried to impose the vaccinomics approach for designing a common peptide vaccine candidate against the immunogenic SigA ofShigellaspp. At first, 44 SigA proteins from different variants ofS. flexneri,S. dysenteriae,S. boydii, andS. sonneiwere assessed to find the most antigenic protein. We retrieved 12 peptides based on the highest score for human leukocyte antigen (HLA) supertypes analysed by NetCTL. Initially, these peptides were assessed for the affinity with MHC class I and class II alleles, and four potential core epitopes VTARAGLGY, FHTVTVNTL, HTTWTLTGY, and IELAGTLTL were selected. From these, FHTVTVNTL and IELAGTLTL peptides were shown to have 100% conservancy. Finally, IELAGTLTL was shown to have the highest population coverage (83.86%) among the whole world population. In vivo study of the proposed epitope might contribute to the development of functional and unique widespread vaccine, which might be an operative alleyway to thwart dysentery from the world.

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Unique Substrate Specificity of SplE Serine Protease from Staphylococcus aureus

Structure ◽

10.1016/j.str.2018.02.008 ◽

2018 ◽

Vol 26 (4) ◽

pp. 572-579.e4 ◽

Cited By ~ 7

Author(s):

Natalia Stach ◽

Magdalena Kalinska ◽

Michal Zdzalik ◽

Radoslaw Kitel ◽

Abdulkarim Karim ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Substrate Specificity ◽

Serine Protease

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Screening of secondary metabolites, bioactive compounds, in vitro antioxidant, antibacterial, antidiabetic and anti-inflammatory activities of chia seeds (Salvia hispanica L.)

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.01088 ◽

2021 ◽

pp. 6289-6294

Author(s):

Saffiya Banu. A ◽

Sheila John ◽

Sarah Jane Monica ◽

Saraswathi. K ◽

Arumugam. P

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Fatty Acids ◽

Staphylococcus Aureus ◽

Antibacterial Activity ◽

Type 2 Diabetes Mellitus ◽

Dpph Radical ◽

Anti Inflammatory

Recent research studies indicate the role of functional foods in preventing the development of complications associated with type 2 diabetes mellitus. Chia seeds are an excellent source of dietary fibre, essential fatty acids, micronutrients and non-nutritive components. The objective of the study was to evaluate the antioxidant, antibacterial, antidiabetic and anti-inflammatory potential of chia seeds. TPC and TFC were estimated using Folin-Ciocalteu Reagent and Alumininum Chloride method. The antioxidant activity was determined using DPPH● radical, ABTS●+ radical, Superoxide (O2-) radical, Fe3+ reducing and phosphomolybdenum reduction assay. Agar well diffusion method was used to determine the antibacterial activity against Escherichia coli, Proteus vulgaris, Shigella flexneri, Micrococcus luteus, Bacillus subtilis and Staphylococcus aureus. Antidiabetic and anti-inflammatory activities were evaluated using alpha amylase inhibition assay and heat induced haemolysis method. Volatile functional compounds were identified using Gas chromatography mass spectrometry. Upon quantification, TPC and TFC were found to be 850.67±14.14µg/mg GAE and 171.21±12.86µg/mg QE. Free radical scavenging activity of chia seeds was ranked in the order of DPPH● radical >ABTS●+ radical > Superoxide (O2-) radical. The capability of chia seeds to function as electron donors was evident through its strong reducing power. With regard to antibacterial activity, maximum inhibition was observed for Staphylococcus aureus, with a zone of inhibition of 31mm at 500µg/mL. Results of antidiabetic assay highlighted the alpha amylase inhibitory action of chia seeds with an IC50 value of 121.46µg/mL. The anti-inflammatory activity of chia seeds increased linearly in a dose dependent manner. GC-MS analysis showed the presence of functionally active compounds such as coumarine, napthoquinone, phytol, fatty acids, flavone and flavone derivatives. Findings of the study highlight that chia seeds have several essential therapeutic properties. Furthermore, clinical studies are required to validate the role of chia seeds in preventing the development of complications associated with type 2 diabetes mellitus.

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Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium

Nature Communications ◽

10.1038/s41467-020-18781-2 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 3

Author(s):

Satria P. Sajuthi ◽

Peter DeFord ◽

Yingchun Li ◽

Nathan D. Jackson ◽

Michael T. Montgomery ◽

...

Keyword(s):

Airway Epithelium ◽

Host Responses ◽

Interferon Response ◽

Host Proteins ◽

Factors Affecting ◽

Mediated Effects ◽

Emerging Virus ◽

Airway Responses

Abstract Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, an emerging virus that utilizes host proteins ACE2 and TMPRSS2 as entry factors. Understanding the factors affecting the pattern and levels of expression of these genes is important for deeper understanding of SARS-CoV-2 tropism and pathogenesis. Here we explore the role of genetics and co-expression networks in regulating these genes in the airway, through the analysis of nasal airway transcriptome data from 695 children. We identify expression quantitative trait loci for both ACE2 and TMPRSS2, that vary in frequency across world populations. We find TMPRSS2 is part of a mucus secretory network, highly upregulated by type 2 (T2) inflammation through the action of interleukin-13, and that the interferon response to respiratory viruses highly upregulates ACE2 expression. IL-13 and virus infection mediated effects on ACE2 expression were also observed at the protein level in the airway epithelium. Finally, we define airway responses to common coronavirus infections in children, finding that these infections generate host responses similar to other viral species, including upregulation of IL6 and ACE2. Our results reveal possible mechanisms influencing SARS-CoV-2 infectivity and COVID-19 clinical outcomes.

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