Signaling pathways underlying TGF-ß mediated suppression of IL-12A gene expression in monocytes.
Mol Immunol
; 166: 101-109, 2024 Feb.
Article
de En
| MEDLINE
| ID: mdl-38278031
ABSTRACT
Transforming growth factor-ß (TGF-ß) is a pleiotropic cytokine essential for multiple biological processes, including the regulation of inflammatory and immune responses. One of the important functions of TGF-ß is the suppression of the proinflammatory cytokine interleukin-12 (IL-12), which is crucial for mounting an anti-tumorigenic response. Although the regulation of the IL-12p40 subunit (encoded by the IL-12B gene) of IL-12 has been extensively investigated, the knowledge of IL-12p35 (encoded by IL-12A gene) subunit regulation is relatively limited. This study investigates the molecular regulation of IL-12A by TGF-ß-activated signaling pathways in THP-1 monocytes. Our study identifies a complex regulation of IL-12A gene expression by TGF-ß, which involves multiple cellular signaling pathways, such as Smad2/3, NF-κB, p38 and JNK1/2. Pharmacological inhibition of NF-κB signaling decreased IL-12A expression, while blocking the Smad2/3 signaling pathway by overexpression of Smad7 and inhibiting JNK1/2 signaling with a pharmacological inhibitor, SP600125, increased its expression. The elucidated signaling pathways that regulate IL-12A gene expression potentially provide new therapeutic targets to increase IL-12 levels in the tumor microenvironment.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Facteur de croissance transformant bêta
/
Sous-unité p35 de l'interleukine-12
Type d'étude:
Prognostic_studies
Limites:
Humans
Langue:
En
Journal:
Mol Immunol
/
Mol. immunol
/
Molecular immunology
Année:
2024
Type de document:
Article
Pays d'affiliation:
Australie
Pays de publication:
Royaume-Uni