SHP2 inhibitor PHPS1 regulates macrophage-adipocyte interaction.

Objective: The objective of this study was to analyze the anti-inflammatory effects of the Src Homology 2 Containing Protein Tyrosine Phosphatase 2(SHP2) inhibitor phenylhydrazono pyrazolone sulfonate1 (PHPS1) by constructing a co-culture system of adipocytes and macrophages using Transwell co-culture plates.Methods: A co-culture of 3T3-L1 adipocytes and RAW 264.7. macrophages was exposed to LPS to induce insulin resistance in adipocytes, followed by treatment with the SHP2 inhibitor PHPS1. After 24 h, analysis of insulin sensitivity and inflammatory response showed that PHPS1 effectively reduced cytokine levels measured by ELISAs and mRNA expression levels of iNOS and COX-2, as assessed by through real-time PCR. Western blotting detected a decrease in NF-κB (pp65/pIkkα) phosphorylation pathway expression and an increase in pIRS-1(Ser 307)/Glut-4 expression levels, indicating its protective role in improving adipocyte insulin resistance."Results：The SHP2 inhibitor PHPS1 reduced the expression of inflammatory factors in TNF-α -treated group, macrophage-adipocyte co-culture group, and LPS-induced macrophage-adipocyte co-culture group, probably by inhibiting the expression of the NF-κB phosphorylation pathway, thus playing a protective role in improving adipocyte insulin resistance.Results: The SHP2 inhibitor PHPS1 attenuated the expression of inflammatory factors in the TNF-α-treated group, macrophage-adipocyte co-culture group, and LPS-induced macrophage-adipocyte co-culture groups by inhibiting the NF-κB phosphorylation pathway, thereby exerting a protective effect on improving adipocyte insulin resistance.