Induction of C-Mip by IL-17 Plays an Important Role in Adriamycin-Induced Podocyte Damage

Abstract

Background/Aims: Although the disturbance of T lymphocyte and glomerular podocyte exerts a crucial function in the pathogenesis of proteinuria, the potential link is still unclear. Methods: The balance of Treg and Th17 cells, and the expression of IL-17/IL-17R and c-mip were investigated in adrimycin-induced nephropathy (AN) mice. The effect and mechanism of IL-17 on podocyte were explored in cultured podocytes. Results: The proportion of Th17 cells in peripheral blood mononuclear cells, the amount of IL-17 in serum and kidney cortical homogenates, and the expression of IL-17R and c-mip in glomerular podocyte were increased obviously in AN mice. In cultured podocytes, recombinant IL-17 led to an induction of apoptosis and cytoskeletal disorganization, an overproduction of c-mip while down-regulation of phosphor-nephrin, and an increased binding of c-mip to NF-κB/RelA. Silence of c-mip prevented podocyte apoptosis and reduction of phosphor-nephrin by prompting nuclear translocation of NF-κB/RelA in IL-17 treated cells. Persistent activation of NF-κB up-regulated pro-survival protein Bcl-2 and decreased podocyte apoptosis, but had no effect on phosphor-nephrin level. Conclusion: These findings demonstrated that induction of IL-17 released by Th17 cells plays a key role in podocytopathy most likely through down-regulation of phosphor-nephrin and Bcl-2 level via overproduction of c-mip.

Response Gene to Complement-32 Promotes the Imbalance of Treg/Th17 in Patients with Dilated Cardiomyopathy

“…Th17 cells function as the important mediators during the pathogenesis of chronic inflammatory disorders via the production of IL-17, IL-21 and IL-22 [30]. These cells and cytokines are involved in the pathogenesis of MS, adrimycin-induced nephropathy, and other autoimmune diseases [31][32][33][34][35][36][37], and promote the progression to DCM [15]. In contrast, Treg cells inhibit the immune response, inflammation, and tissue destruction by producing the anti-inflammatory cytokines (TGF-βand IL-10) and suppressing the function of other lymphocytes [38,39].…”

High Glucose-Induced Podocyte Injury Involves Activation of Mammalian Target of Rapamycin (mTOR)-Induced Endoplasmic Reticulum (ER) Stress

“…As previously described [22], immobilized mouse podocytes (a kind gift from Prof. Peter Mundel) were cultured at 33oC in RPMI1640 media containing fetal bovine serum (10%, Invitrogen) and recombinant mouse interferon-γ (10U/ml, Sigma-Aldrich-Aldrich). Following overnight serum starvation, the medium was replaced with RPMI1640 containing normal glucose (NG: 5.6 mM) or high glucose (HG: 30 mM).…”

Change of Peripheral Blood Treg/Thl7 in Cognitive Impairment with Chronic Renal Failure Patients

“…They promote inflammation in the body through the secretion of IL-17, IL-23, IL-6 and other cytokines, and are closely associated with autoimmune diseases, chronic infection and tumours [8]. The Treg/Th17 balance plays a key role in maintaining the stability of the immune state [9, 10]. An imbalance can cause a series of immune inflammatory responses that are characteristic of cancer, autoimmune diseases, atherosclerosis, allergic asthma and diseases of the development process [11-15].…”