دورية أكاديمية
أعرض في EDS

Production and Release of Proinflammatory Mediators by the Cockroach Allergen Bla g 1 via a Shared Membrane-Destabilization Mechanism.

التفاصيل البيبلوغرافية
العنوان: Production and Release of Proinflammatory Mediators by the Cockroach Allergen Bla g 1 via a Shared Membrane-Destabilization Mechanism.
المؤلفون: Foo ACY; Dept. of Chemistry, St. Francis Xavier University, Antigonish, Nova Scotia B2G 2W5, Canada., Edin ML; Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Science, Research Triangle Park, North Carolina 27709, United States., Lin WC; Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Science, Research Triangle Park, North Carolina 27709, United States., Lih FB; Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Science, Research Triangle Park, North Carolina 27709, United States., Gabel SA; Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Science, Research Triangle Park, North Carolina 27709, United States., Uddin MN; Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Science, Research Triangle Park, North Carolina 27709, United States., Fessler MB; Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Science, Research Triangle Park, North Carolina 27709, United States., Zeldin DC; Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Science, Research Triangle Park, North Carolina 27709, United States., Mueller GA; Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Science, Research Triangle Park, North Carolina 27709, United States.
المصدر: Biochemistry [Biochemistry] 2024 Jul 16; Vol. 63 (14), pp. 1730-1737. Date of Electronic Publication: 2024 Jun 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370623 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4995 (Electronic) Linking ISSN: 00062960 NLM ISO Abbreviation: Biochemistry Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, American Chemical Society.
مواضيع طبية MeSH: Cell Membrane*/metabolism , Cockroaches*/immunology , Cockroaches*/metabolism , Allergens*/metabolism , Allergens*/immunology, Animals ; Humans ; Inflammation Mediators/metabolism ; Interleukin-1beta/metabolism ; Phospholipases A2/metabolism ; Phospholipases A2/immunology ; HSP70 Heat-Shock Proteins/metabolism ; Fatty Acids, Unsaturated/metabolism ; Insect Proteins/metabolism ; Insect Proteins/chemistry
مستخلص: The cockroach allergen Bla g 1 encloses an exceptionally large hydrophobic cavity, which allows it to bind and deliver unsaturated fatty acid ligands. Bla g 1-mediated delivery of naturally occurring (nMix) ligands has been shown to destabilize lipid membranes, contributing to its digestive/antiviral functions within the source organism. However, the consequences of this activity on Bla g 1 allergenicity following human exposure remain unknown. In this work, we show that Bla g 1-mediated membrane disruption can induce a proinflammatory immune response in mammalian cells via two complementary pathways. At high concentrations, the cytotoxic activity of Bla g 1 induces the release of proinflammatory cytosolic contents including damage-associated molecular patterns (DAMPs) such as heat-shock Protein-70 (HSP70) and the cytokine interleukin-1 (IL-1β). Sublytic concentrations of Bla g 1 enhanced the ability of phospholipase A2 (PLA 2 ) to extract and hydrolyze phospholipid substrates from cellular membranes, stimulating the production of free polyunsaturated fatty acids (PUFAs) and various downstream inflammatory lipid mediators. Both of these effects are dependent on the presence of Bla g 1's natural fatty-acid (nMix) ligands with CC 50 values corresponding to the concentrations required for membrane destabilization reported in previous studies. Taken together, these results suggest that mechanisms through which Bla g 1-mediated lipid delivery and membrane destabilization could directly contribute to cockroach allergic sensitization.
المشرفين على المادة: 0 (allergen Bla g 1)
0 (Allergens)
0 (Inflammation Mediators)
0 (Interleukin-1beta)
EC 3.1.1.4 (Phospholipases A2)
0 (HSP70 Heat-Shock Proteins)
0 (Fatty Acids, Unsaturated)
0 (Insect Proteins)
تواريخ الأحداث: Date Created: 20240625 Date Completed: 20240716 Latest Revision: 20240716
رمز التحديث: 20240716
DOI: 10.1021/acs.biochem.3c00631
PMID: 38915291
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-4995
DOI:10.1021/acs.biochem.3c00631