Role of TGF-β activated kinase-1 inhibitor on the interaction between macrophages and mesangial cells on the condition of high glucose

ABSTRACT

Objective

To investigate the effect of TGF-β activated kinase-1(TAK1) inhibitor 5Z-7-oxozeaenol on the interaction between macrophages and mesangial cells exposed to high glucose.

Methods

The macrophages and mesangial cells were cultured separately or co-cultured and divided into seven groups: inhibitor control group, mannitol control group, normal control group, high glucose group and inhibitor groups. The expression of p-TAK1, TAK1 binding protein (TAB1), transcription factor NF - κ B (NF-κB p65) of macrophages were analyzed by Western blotting. The intracellular localization of NF-κB p65 was analyzed by immunofluorescence. The levels of inflammation cytokines and extracellular matrix were determined by enzyme-linked immune sorbent assay. Migration of macrophages was observed by microscope.

Results

Compared with control group, the expression of p-TAK1, TAB1, NF-κB p65 were significantly higher in high glucose group (P < 0.05). Both in co-culture group and single culture group, the levels of inflammation cytokines and extracellular matrix (P < 0.05) in high glucose group were higher than that in control group. Exposed to high glucose, the levels of inflammation cytokines and extracellular matrix in co-cultured group were higher than that in single culture group (P < 0.05). 5Z-7-oxozeaenol can decrease those cytokines secretion, comparing with high glucose group (P < 0.05). The number of macrophages migration were decreased by 5Z-7-oxozeaenol (P < 0.05).

Conclusion

Exposed to high glucose, macrophages and mesangial cells can interact with each other to promote the secretion of inflammation cytokines and extracellular matrix. TAK1 inhibitor can reduce the secretion of inflammation cytokines and extracellular matrix components by intervening NF-κB p65 nuclear transfer and inhibiting macrophage migration.

KEYWORDS:

• Co-culture
• diabetic nephropathy
• fibrosis
• inflammation
• TGF-β activated kinase-1

Declaration of interest

The authors declare no conflict of interests.

Additional information

Funding

This study was generously supported by the National Natural Science Foundation of China (No. 81270813).