BALB/c and C57BL/6 mice differ in oxidant and antioxidant responses in innate and adaptive immune cells in an asthma model induced by cockroach allergens.

Autor: Al-Kharashi LA; Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alqarni SA; Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Ahmad SF; Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Al-Harbi NO; Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alsanea S; Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Ibrahim KE; Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia., Algahtani MM; Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alhazzani K; Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Shazly GA; Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Al-Harbi MM; Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Nadeem A; Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: anadeem@ksu.edu.sa.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2023 Nov; Vol. 124 (Pt B), pp. 110892. Date of Electronic Publication: 2023 Sep 15.
DOI: 10.1016/j.intimp.2023.110892
Abstrakt: Asthma is a complex and heterogenous disease affected by a multitude of factors. Several phenotypes of asthma exist which are influenced by various molecular mechanisms that include presence of antioxidant and oxidant enzymes in different immune cells such as dendritic cells (DCs), alveolar macrophages (AMs), neutrophils, and T cells. Close interaction between epithelial cells and dendritic cells initiates complex pathogenesis of asthma followed by involvement of other innate and adaptive immune cells. In chronic phase of the disease, these immune cells support each other in amplification of airway inflammation where oxidant-antioxidant balance is known to be an important contributing factor. Genetic variability in antioxidant response may influence the development of airway inflammation, however it has not been studied in mice yet. The two most studied mice strains, i.e. BALB/c and C57BL/6 are reported to have dissimilar airway responses to the same allergens due to their genetic makeup. In this investigation, we explored whether these strains had any differences in pulmonary oxidant-antioxidant system (Nrf2, SOD2, iNOS, HO-1, nitrotyrosine) in different immune cells (DCs, AMs, neutrophils, T cells), airway inflammation (presence of eosinophils and/or neutrophils) and mucus production in response to repeated cockroach allergen extract (CE) mouse model of asthma. Our data show that C57BL/6 mice had better induction of antioxidant system than BALB/c mice. Consequently, iNOS/nitrotyrosine levels were much exaggerated in BALB/c than C57BL/6 mice. As a result, BALB/c mice developed mixed granulocytic airway inflammation, whereas C57BL/6 developed mostly eosinophilic airway inflammation. Our data suggest that an exaggerated oxidant generation along with a weak antioxidant induction in response to a natural allergen on a susceptible genetic background may determine development of severe asthma phenotype such as mixed granulocyte inflammation.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: