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  • ACTH4-10 protects the ADR-injured podocytes by stimulating B lymphocytes to secrete interleukin-10.

ACTH4-10 protects the ADR-injured podocytes by stimulating B lymphocytes to secrete interleukin-10.

International immunopharmacology (2020-07-19)
Kun Wang, Huaping Du, Zhen Chen, Hao Lu, Renfang Xu, Dong Xue
ABSTRACT

In the present study, we aimed to assess whether adrenocorticotropic hormone (ACTH) could protect the podocytes from adriamycin (ADR)-induced injury by stimulating B lymphocytes to secrete the associated cytokines. Proliferation assay was used to assess the proliferation and activity of podocytes. Enzyme-linked immunosorbent assay was used to examine the secretion of IL-10 and IL-4. TUNEL apoptosis detection kit was used to detect the apoptosis of podocytes. Real-time PCR and Western blotting analysis were used to examine the expressions of nephrin and podocin at the mRNA and protein levels. Compared with the normal control group, the podocyte proliferation of ADR group was significantly inhibited. However, compared with the ADR group, the podocyte proliferation of the supernatant (1 µg/L, 10 µg/L or 100 µg/L ACTH4-10) + ADR groups was generally increased, and the pro-proliferative effect of the supernatant containing 10 µg/L ACTH4-10 was the highest. Moreover, we found that after B lymphocytes were intervened by 10 µg/L ACTH4-10, the IL-10 level in the cell supernatant was significantly elevated (p < 0.05). When anti-IL-10R was added, the podocyte proliferation of the supernatant (10 µg/L ACTH4-10) + ADR group was significantly inhibited. Furthermore, the supernatant of B cells stimulated with 10 µg/L ACTH4-10 could better decrease the apoptosis rate of injured podocytes and increase the expressions of nephrin and podocin at the mRNA and protein levels by elevating the secretion of IL-10. Compared with ACTH4-10, the supernatant of B cells stimulated with ACTH4-10 could better protect the podocytes from ADR-induced injury by elevating the secretion of IL-10.