Butyrate and propionate induced activated or non-activated neutrophil apoptosis via HDAC inhibitor activity but without activating GPR-41/GPR-43 pathways

被引:186
作者
Aoyama, Michiko [1 ]
Kotani, Joji [2 ]
Usami, Makoto [1 ,3 ]
机构
[1] Kobe Univ, Div Nutr & Metab, Dept Biophys, Grad Sch Hlth Sci, Kobe, Hyogo 657, Japan
[2] Hyogo Coll Med, Dept Emergency & Crit Care Med, Nishinomiya, Hyogo, Japan
[3] Kobe Univ Hosp, Dept Nutr, Kobe, Hyogo, Japan
基金
日本学术振兴会;
关键词
Short-chain fatty acids; G-protein receptors; Mitogen-activated protein kinases; Lipopolysaccharide; Tumor-necrosis factor-alpha; a1; CHAIN FATTY-ACIDS; SODIUM-BUTYRATE; EXPRESSION; TRICHOSTATIN; METHYLATION; RESPONSES; SEPSIS; CANCER; DOMAIN; CELLS;
D O I
10.1016/j.nut.2009.07.006
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Objective: Decreased neutrophil apoptosis is implicated in persistent inflammation resulting in systemic inflammatory response syndrome and multiple organ dysfunctions syndromes. Short-chain fatty acids (SCFAs) may be a candidate to control neutrophil apoptosis because SCFAs are normally produced in the gut and related products have been approved for human use. We investigated the effects of SCFAs on apoptosis of activated and non-activated neutrophils and their mechanisms. Methods: Purified neutrophils obtained from healthy volunteers were preincubated for 1 h with or without the G-protein receptor (GPR) inhibitor pertussis toxin (100 ng/mL) or U-73122 (50 ng/mL), extracellular signal-related protein kinase inhibitor PD98059 (10 mu M), mitogen-activated protein kinase (MAPK) p38 inhibitor SB203580 (25 mu M), Jun kinase inhibitor-I (2 mu M), caspase-3 and -7 inhibitor Z-VAD-FMK (100 mu M), caspase-8 inhibitor Z-IETD-FMK (50 mu M), or caspase-9 inhibitor Z-LEHD-FMK (50 mu M). The cells were then cultured with or without SCFAs or trichostatin A, a typical histone deacetylase inhibitor, in the presence or absence of lipopolysaccharide (1 mu g/mL) or tumor necrosis factor-alpha (100 ng/mL). Neutrophil apoptosis was assessed by annexin V staining using flow cytometry. The GPR-41 and -43 and apoptosis-related proteins (bax, mcl-1, a1) mRNA were measured by quantitative real-time polymerase chain reaction and the expression of acetylated histone H3 was determined by western blot. Results: The caspase inhibitors inhibited butyrate- and propionate-induced neutrophil apoptosis treated or untreated with lipopolysaccharide or tumor necrosis factor-alpha, whereas GPR and MAPK inhibitors had no effect. The mRNA expressions of GPR-43 and a1 protein were reduced by butyrate and propionate: The expressions of acetylated histone H3 were induced by butyrate and propionate. Conclusion: These results suggest that butyrate and propionate increase apoptosis of neutrophils irrespective of their activation state, by factors other than GPRs and MAPKs, and their mechanisms likely relate to their histone deacetylase inhibition activity, which may control a1mRNA expression. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:653 / 661
页数:9
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