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Inflammation. 2016 Feb;39(1):172-181. doi: 10.1007/s10753-015-0236-8.

TLR4-MyD88-TRAF6-TAK1 Complex-Mediated NF-κB Activation Contribute to the Anti-Inflammatory Effect of V8 in LPS-Induced Human Cervical Cancer SiHa Cells.

Author information

1
Department of Gynecology Oncology, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China. heaiqinnantong@163.com.
2
Department of Gynecology Oncology, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China.
3
Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China. xuyunzhaonantong@163.com.

Abstract

The synthetic compound 7-4-[Bis-(2-hydroxyethyl)-amino]-butoxy-5-hydroxy-8-methoxy-2-phenylchromen-4-one (V8) is a novel flavonoid-derived compound. In this study, we investigated the effects of V8 on Toll-like receptor 4 (TLR4)-mediated inflammatory reaction in human cervical cancer SiHa cells and lipopolysaccharide (LPS)-induced TLR4 activity in cervical cancer SiHa (HPV16+) cells, but not in HeLa (HPV18+) and C33A (HPV-) cells. In addition, V8 inhibited LPS-induced expression of TLR4, MyD88, TRAF6 and phosphorylation of TAK1, and their interaction with TLR4 in SiHa cells, resulting in an inhibition of TLR4-MyD88-TRAF6-TAK1 complex. Moreover, V8 blocked LPS-induced phosphorylation of IκB and IKK, resulting in inhibition of the nuclear translocation of P65-NF-κB in SiHa cells. We also found that V8 reduced the expression of NF-κB target genes, such as those for COX-2, iNOS, IL-6, IL-8, CCL-2, and TNF-α in LPS-stimulated SiHa cells. These results suggested that V8 exerted an anti-inflammatory effect on SiHa cells by inhibiting the TLR4-MyD88-TRAF6-TAK1 complex-mediated NF-κB activation.

KEYWORDS:

HPV16; NF-κB; TLR4; V8; cervical cancer; inflammation

PMID:
26276130
DOI:
10.1007/s10753-015-0236-8
[Indexed for MEDLINE]

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