TLR2-ERK signaling pathway regulates expression of galectin-3 in a murine model of OVA-induced allergic airway inflammation

Yunxiang Lv; Guiyun Jiang; Yanru Jiang; Caiqiu Peng; Wei Li

doi:10.1016/j.toxlet.2024.05.008

TLR2-ERK signaling pathway regulates expression of galectin-3 in a murine model of OVA-induced allergic airway inflammation

Toxicol Lett. 2024 May 14:S0378-4274(24)00095-X. doi: 10.1016/j.toxlet.2024.05.008. Online ahead of print.

Authors

Yunxiang Lv¹, Guiyun Jiang², Yanru Jiang³, Caiqiu Peng³, Wei Li⁴

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical University, Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease; Molecular Diagnosis Center, Bengbu, Anhui, 233000, China. Electronic address: yunxianglv@126.com.
² Department of Clinical laboratory, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, Anhui, China.
³ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical University, Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease; Molecular Diagnosis Center, Bengbu, Anhui, 233000, China.
⁴ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical University, Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease; Molecular Diagnosis Center, Bengbu, Anhui, 233000, China. Electronic address: bbmcliwei@126.com.

PMID: 38754639
DOI: 10.1016/j.toxlet.2024.05.008

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.

Keywords: Allergic airway inflammation; Extracellular regulated kinase; Galectin-3; Toll-like receptor 2.