IL-1β functionally attenuates ABCG2 and PDZK1 expression in HK-2 cells partially through NF-ĸB activation.

Abstract

Long-standing untreated hyperuricemia could lead to gout. Several recent studies have demonstrated a significant decrease of serum urate during acute gout attack, which is an aseptic inflammation process focusing on IL-1β. However, how IL-1β, by itself, alters the expression and the functional activity of urate transporters in renal tubular epithelial cells is still unclear. Herein, we revealed that IL-1β could attenuate the mRNA and protein levels of ABCG2, a major urate efflux pump, in HK-2 cells by real-time PCR and Western-blot assays. Moreover, using an ABCG2 specific inhibitor and a new sensitive and specific detection system, it was found that IL-1β also reduced the ABCG2 transporter activities. Incubation with specific inhibitors of the NF-κB pathway partly dampened the inhibitory effect of IL-1β on ABCG2, indicating that IL-1β reduced the ABCG2 expression partially through the NF-ĸB pathway. Furthermore, the decreased expression of PDZK1 induced by IL-1β, which is dependent on the NF-κB pathway, could account for the imbalance between the functions and expressions of ABCG2 on this status. These findings demonstrated a new role for IL-1β, whereby it leads to the inhibition of ABCG2 in renal tubular epithelial cells; this new role probably does not encompass its involvement in the process of renal urate excretion mediated by inflammation. Therefore, other regulation mechanisms of urate reabsorption in renal tubular epithelial cells deserve to be examined in further studies.

• Authors: Xiaoyong Lu, Mo Chen, Jingfang Shen, Yujia Xu, Huaxiang Wu
• Journal: Cell biology international (Cell Biol Int) Vol. 43 Issue 3 Pg. 279-289 (Mar 2019) ISSN: 1095-8355 [Electronic] England
• PMID: 30632646 (Publication Type: Journal Article)
• Copyright: © 2019 International Federation for Cell Biology.

Chemical References

• 3-(4-methylphenylsulfonyl)-2-propenenitrile
• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• Carrier Proteins
• Interleukin-1beta
• Membrane Proteins
• NF-kappa B
• Neoplasm Proteins
• Nitriles
• PDZK1 protein, human
• RNA, Messenger
• Sulfones
• Thiocarbamates
• prolinedithiocarbamate
• Uric Acid
• Proline

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 2 (genetics, metabolism)
• Base Sequence
• Biological Transport (drug effects)
• Carrier Proteins (metabolism)
• Cell Line
• Humans
• Interleukin-1beta (pharmacology)
• Membrane Proteins
• NF-kappa B (metabolism)
• Neoplasm Proteins (genetics, metabolism)
• Nitriles (pharmacology)
• Polymorphism, Single Nucleotide (genetics)
• Proline (analogs & derivatives, pharmacology)
• RNA, Messenger (genetics, metabolism)
• Sulfones (pharmacology)
• Thiocarbamates (pharmacology)
• Time Factors
• Uric Acid (metabolism)