IκB激酶
肿瘤坏死因子α
脂多糖
NF-κB
内分泌学
NFKB1型
信号转导
内科学
六烯酸
化学
炎症
αBκ
生物
药理学
医学
生物化学
转录因子
多不饱和脂肪酸
脂肪酸
基因
作者
Dilsah Ezgi Yilmaz,Sefika Pinar Senol,Meryem Temiz-Reşitoğlu,Seyhan Şahan-Fırat,Bahar Tunçtan
出处
期刊:Cellular and Molecular Biology
日期:2023-09-30
卷期号:69 (9): 15-23
被引量:2
标识
DOI:10.14715/cmb/2023.69.9.3
摘要
The nucleotide-binding oligomerization domain-like receptor X1 (NLRX1) has been associated with various anti-inflammatory mechanisms. We investigated whether the NLRX1 ligand docosahexaenoic acid (DHA) ameliorates lipopolysaccharide (LPS)-induced inflammatory hyperalgesia by interacting with tumor necrosis factor receptor-associated factor 6 (TRAF6)/inhibitor of kB (IkB) kinase (IKK)/IkB-a/nuclear factor-κB (NF-κB) signaling pathway in the central nervous system. Reaction time to thermal stimuli within 30 seconds was measured in male mice injected with saline, lipopolysaccharide (LPS), and/or DHA after 6 hours using the hot plate test. Co-immunoprecipitation and immunoblotting studies were performed to determine the activation of the TRAF6/IKK/IkB-a/NF-kB pathway in the brains and spinal cords of animals. Latency to the thermal stimulus was reduced by 30% in LPS-injected endotoxemic mice compared with saline-injected mice. Treatment with DHA significantly improved latency compared with endotoxemic mice. In the brain and spinal cord of LPS-injected mice, treatment with DHA also prevented the increase in the expression and/or activity of (1) IKKa/IKKβ, IKKg, and K63 U in the NLRX1-immunoprecipitated tissues, (2) IKKa/IKKβ, K63 U, and K48 U in the IKKg-immunoprecipitated tissues, and (3) IkB-α, NF-kB p65, and interleukin-1β associated with decreased IkB-α expression. These findings suggest that inhibition of IKK/IkB-a/NF-kB signaling by dissociation of NLRX1 from TRAF6 in response to LPS treatment contributes to the protective effect of DHA against inflammatory hyperalgesia.
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