Galectin-9 Induces Il-1Β Production As a Key Inflammatory Cytokine in the Acute Myeloid Leukemia Cell Line (U937) Publisher



N Behranvand NAFISEH ; F Nasri FARZAD ; Mv Moghaddam Maryam VAKILI ; Md Gholami Mohammad DAVOODZADEH ; E Safari ELAHEH ; N Esmaeil NAFISEH ; R Falak REZA
Source: Research in Pharmaceutical Sciences Published:2025

Abstract

Background and purpose: T-cell immunoglobulin and mucin-domain containing protein-3 (TIM-3)/ galectin-9 (Gal-9)/ autocrine loop in myeloid leukemia stem cells provokes inflammation through the NF-κB signaling pathway, which is influential in the expression of inflammatory factors. Interleukin 1β (IL-1β) is a vital inflammatory cytokine that plays an important role in the proliferation and therapy resistance of acute myeloid leukemia (AML) cells. This study aimed to assess the effect of Gal-9 on IL-1β in the human leukemic U937 cell line. Experimental approach: The U937 cells were cultured in different concentrations of Gal-9. Cell counting kit-8 was used to assess the effect of Gal-9 on human leukemic U937 cell proliferation. Also, its impact on the expression of TIM-3, Gal-9, IL-1β, IL-1βR, IL-1βRAP, and NLRP3 genes and IL-1β protein was studied by RT-PCR and ELISA, respectively. Moreover, the effect of Gal-9 on the NF-κB signaling pathway was evaluated by western blotting. Findings/Results: U937 cells were expanded in the presence of Gal-9 in a concentration-dependent manner. Following treatment of U937 cells with Gal-9, the gene expression of Gal-9, IL-1B, IL-1BR, and IL-1BRAP were significantly upregulated compared to the control group. The IL-1β concentration increased following Gal-9 treatment in a concentration-dependent manner, while following time-pass its level significantly decreased. Furthermore, Gal-9 slightly increased NF-κB phosphorylation. Conclusion and implications: Gal-9 increased IL-1β level as a critical inflammatory cytokine in the proliferation and resistance of AML cells to therapy. According to this finding, targeting and blocking the TIM-3/Gal-9 autocrine loop can suppress IL-1β production and facilitate AML treatment. © 2025 Elsevier B.V., All rights reserved.