TLR2-ERK signaling pathway regulates expression of galectin-3 in a murine model of OVA-induced allergic airway inflammation.
Toxicol Lett
; 397: 55-66, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38754639
ABSTRACT
Toll-like receptor 2 (TLR2) and galectin-3 (Gal-3) are involved in the pathological process of asthma, but the underlying mechanism is not fully understood. We hypothesized that TLR2 pathway may regulate expression of Gal-3 in allergic airway inflammation. Wild-type (WT) and TLR2-/- mice were sensitized on day 0 and challenged with ovalbumin (OVA) on days 14-21 to establish a model of allergic airway inflammation, and were treated with a specific ERK inhibitor U0126. Histological changes in the lungs were analyzed by hematoxylin-eosin (HE) and Periodic Acid-Schiff (PAS) staining; cytokines and anti-OVA immunoglobulin E (IgE) were tested by ELISA; and related protein expression in lung tissues was measured by western blot. We found that the expression levels of TLR2 and Gal-3 markedly increased concomitantly with airway inflammation after OVA induction, while TLR2 deficiency significantly alleviated airway inflammation and reduced Gal-3 expression. Moreover, the expression levels of phosphorylated mitogen-activated protein kinases (p-MAPKs) were significantly elevated in OVA-challenged WT mice, while TLR2 deficiency only significantly decreased phosphorylated extracellular signal-regulated kinase (p-ERK) levels. Furthermore, we found that U0126 treatment significantly alleviated allergic airway inflammation and decreased Gal-3 levels in OVA-challenged WT mice, but had no further effect in OVA-challenged TLR2-/- mice. These above results suggested that TLR2 is an upstream signal molecule of ERK. We further demonstrated that TLR2 regulates Gal-3 expression through the ERK pathway in LTA-stimulated macrophages in vitro. Our findings showed that the TLR2-ERK signaling pathway regulates Gal-3 expression in a murine model of allergic airway inflammation.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Ovalbumina
/
Sistema de Sinalização das MAP Quinases
/
Galectina 3
Limite:
Animals
Idioma:
En
Revista:
Toxicol Lett
/
Toxicol. lett
/
Toxicology letters
Ano de publicação:
2024
Tipo de documento:
Article