Issue Archive

Advanced glycated albumin induces macrophage pyroptosis via upregulating nucleotide-binding oligomerization domain-like receptor protein 3

ZHANG Zhao-Qiang¹, YANG Yi-Fan², YAN Jing-Rui¹, YU Fei¹, WANG Xiao-Xu¹, WANG Zhi-Chao³, TIAN Hua⁴, YAO Shu-Tong^1,*

¹College of Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, China；²College of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, China；³College of Nursing, Shandong First Medical University & Shandong Academy of Medical ciences, Taian 271000, China；⁴Institute of Atherosclerosis, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, China

Abstract

The purpose of the present study was to investigate the effect of advanced glycated albumin (AGE-alb) on pyroptosis of macrophages and the underlying molecular mechanisms. RAW264.7 macrophages were treated with AGE-alb (1, 2, 4 and 6 g/L) and control albumin (C-alb, 4 g/L) for 24 h, or preincubated with MCC950 (1 μmol/L) for 1 h and then treated with AGE-alb (4 g/L) for 24 h. Cell viability and caspase-1 activity were measured by MTT and assay kits, respectively. Lactate dehydrogenase (LDH) activity and the levels of interleukin-1β (IL-1β) and IL-18 in media were detected. Cell death degree was evaluated by TUNEL and Hoechst 33342/PI staining. The protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), procaspase-1 and cleaved caspase-1 were assessed by Western blot. The results showed that AGE-alb treatment caused obvious decrease in cell viability and increases in LDH leakage and the percentages of TUNEL- or PI-positive cells in a concentration-dependent manner. Additionally, AGE-alb promoted IL-1β and IL-18 secretion, upregulated NLRP3 expression, and increased caspase-1 activity especially at the dose of 4 and 6 g/L. However, MCC950 (an NLRP3 inhibitor) pretreatment inhibited significantly the decrease in cell viability and the increases in LDH leakage and percentages of TUNEL- or PI-positive cells induced by AGE-alb. Furthermore, MCC950 attenuated obviously AGE-alb-induced IL-1β and IL-18 secretion and caspase-1 activation. These results indicate that AGE-alb may induce macrophage pyroptosis, and the mechanism is at least partially by activating NLRP3-caspase-1 pathway. 

Key words: advanced glycated albumin; nucleotide-binding oligomerization domain-like receptor protein 3; caspase-1; Macrophage; pyroptosis

Received: 2019-05-14　　Accepted: 2019-09-18

Corresponding author: 姚树桐　　E-mail: yst228@126.com

DOI: 10.13294/j.aps.2019.0072

Citing This Article：

ZHANG Zhao-Qiang, YANG Yi-Fan, YAN Jing-Rui, YU Fei, WANG Xiao-Xu, WANG Zhi-Chao, TIAN Hua, YAO Shu-Tong. Advanced glycated albumin induces macrophage pyroptosis via upregulating nucleotide-binding oligomerization domain-like receptor protein 3. Acta Physiol Sin 2019; 71 (6): 846-854 (in Chinese with English abstract).