Advanced glycated albumin induces macrophage pyroptosis via upregulating nucleotide-binding oligomerization domain-like receptor protein 3.
- Author:
Zhao-Qiang ZHANG
1
;
Yi-Fan YANG
2
;
Jing-Rui YAN
1
;
Fei YU
1
;
Xiao-Xu WANG
1
;
Zhi-Chao WANG
3
;
Hua TIAN
4
;
Shu-Tong YAO
5
Author Information
1. College of Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, China.
2. College of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, China.
3. College of Nursing, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, China.
4. Institute of Atherosclerosis, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, China.
5. College of Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, China. yst228@126.com.
- Publication Type:Journal Article
- MeSH:
Caspase 1;
Gene Expression Regulation;
drug effects;
Interleukin-1beta;
genetics;
Macrophages;
drug effects;
NLR Family, Pyrin Domain-Containing 3 Protein;
genetics;
Pyroptosis;
drug effects;
Serum Albumin;
pharmacology
- From:
Acta Physiologica Sinica
2019;71(6):846-854
- CountryChina
- Language:Chinese
-
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.
