Morita-Baylis-Hillman adduct 2-(3-hydroxy-1-methyl-2-oxoindolin-3-il) acrylonitrile (CISACN) ameliorates the pulmonary allergic inflammation in CARAS model by increasing IFN-γ/IL-4 ratio towards the Th1 immune response

Copyright © 2024 Elsevier B.V. All rights reserved..

Combined allergic rhinitis and asthma syndrome (CARAS) is an airway-type 2 immune response with a profuse inflammatory process widely affecting the world population. Due to the compromise of quality of life and the lack of specific pharmacotherapy, the search for new molecules becomes relevant. This study aimed to evaluate the effectiveness of the Morita-Bailys-Hillman adduct (CISACN) treatment in the CARAS experimental model. Female BALB/c mice were ovalbumin (OVA) -sensitized and -challenged and treated with CISACN. The treatment decreased the eosinophil migration to the nasal and lung cavities and tissues and the goblet cell hyperplasia/hypertrophy, attenuated airway hyperactivity by reducing the hyperplasia/hypertrophy of the smooth muscle and the extracellular matrix's thickness. Also, the treatment reduced the clinical signs of rhinitis as nasal rubbing and sneezing in a histamine-induced nasal hyperreactivity assay. The immunomodulatory effect of CISACN was by reducing OVA-specific IgE serum level, and IL-33, IL-4, IL-13, and TGF-β production, dependent on IFN-γ increase. Furthermore, the effect of CISACN on lung granulocytes was by decreasing the p-p38MAPK/p65NF-κB signaling pathway. Indeed, CISACN reduced the p38MAPK and p65NF-κB activation. These data demonstrated the anti-inflammatory and immunomodulatory effects of the CISACN with scientific support to become a pharmacological tool to treat airway inflammatory diseases.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:130

Enthalten in:

International immunopharmacology - 130(2024) vom: 30. März, Seite 111737

Sprache:

Englisch

Beteiligte Personen:

Adilis Maria Paiva Ferreira, Larissa [VerfasserIn]
Karla Diega Paiva Ferreira, Laércia [VerfasserIn]
Fragoso Pereira Cavalcanti, Raquel [VerfasserIn]
Allysson de Assis Ferreira Gadelha, Francisco [VerfasserIn]
Mangueira de Lima, Louise [VerfasserIn]
Francisco Alves, Adriano [VerfasserIn]
Gabriel Lima Júnior, Cláudio [VerfasserIn]
Regina Piuvezam, Marcia [VerfasserIn]

Links:

Volltext

Themen:

207137-56-2
9006-59-1
Acrylonitrile
Adducts
CARAS experimental model
Clinical rhinitis signs
Cytokines
Eosinophils
Interleukin-4
Journal Article
MP1U0D42PE
Ovalbumin
Th1/Th2 balance

Anmerkungen:

Date Completed 25.03.2024

Date Revised 28.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.intimp.2024.111737

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM368914429