Treponema pallidum FlaA2 inducing the release of pro-inflammatory cytokines is mediated via TLR2 in keratinocytes

Luo, Yuting; Xie, Yanping; Chen, Jiayi; Zhou, Jiahuan; Zhao, Feijun; Liu, Shuangquan; Zeng, Tiebing; Xu, Man; Xiao, Yao

doi:10.1016/j.micpath.2022.105879

Cited by 1 publication

(1 citation statement)

References 53 publications

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“…Our results indicated that HM induced IL-6 via the TLR4/COX-2/PGE2 signaling pathway in the AGS gastric cell line, which agreed with literature demonstrating the production of IL-6 via the activation of TLR4/COX-2/PGE2 pathway both in vitro (i.e., using human coronary artery endothelial cells and tracheal smooth muscle cells) and in vivo (i.e., mouse airways) [ 59 , 60 ]. However, the blockade of TLR4 signaling and COX-2 generation did not fully suppress HM-induced IL-6 secretion, suggesting the involvement of other HM receptors such as TLR2 signaling, reported to mediate inflammatory cytokine release from human monocytes [ 37 ] and keratinocytes [ 61 ]. Further in vitro investigation of HM-induced signaling pathways causing IL-6 production and secretion in gastric epithelial cells by targeting TLR2 should provide more insights.…”

Section: Discussionmentioning

confidence: 99%

Herbal melanin modulates PGE2 and IL-6 gastroprotective markers through COX-2 and TLR4 signaling in the gastric cancer cell line AGS

El-Obeid,

Maashi,

AlRoshody

et al. 2023

BMC Complement Med Ther

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We reported a gastric anti-ulcerogenic effect of the Nigella sativa (L.)-derived herbal melanin (HM) using rat models. However, the molecular mechanisms underlying this HM gastroprotective effect remain unknown. Cyclooxygenase-2 (COX-2)-catalyzed prostaglandin E2 (PGE2) and toll-like receptor 4 (TLR4)-mediated interleukin-6 (IL-6) production and secretion play major roles in gastric mucosal protection. In the current study, the human gastric carcinoma epithelial cell line AGS was used as a model to investigate the effect of HM on TLR4, COX-2, glycoprotein mucin 4 protein and gene expression using immuno-cyto-fluorescence staining, Western blot technology, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Gastroprotective markers PGE2 and IL-6 production and secretion were also assessed using an enzyme-linked immunosorbent assay (ELISA). Bacterial lipopolysaccharides (LPS), well-known inducers of TLR4, COX-2, PGE2 and IL-6 expression, were used as a positive control. We showed that HM upregulated its main receptor TLR4 gene and protein expression in AGS cells. HM increased, in a dose- and time-dependent manner, the secretion of PGE2 and the expression of COX-2 mRNA and protein, which was detected in the nucleus, cytoplasm and predominantly at the intercellular junctions of the AGS cells. In addition, HM enhanced IL-6 production and secretion, and upregulated the mucin 4 gene expression, the hallmarks of gastroprotection. To check whether HM-induced PGE2 and IL-6 through TLR4 signaling and COX-2 generated, AGS cells were pre-treated with a TLR4 signaling inhibitor TAK242 and the COX-2 inhibitor NS-398. A loss of the stimulatory effects of HM on COX-2, PGE2 and IL-6 production and secretion was observed in TAK242 and NS-398-pre-treated AGS cells, confirming the role of TLR4 signaling and COX-2 generated in the HM gastroprotective effects. In conclusion, our results showed that HM enhances TLR4/COX-2-mediated secretion of gastroprotective markers PGE2 and IL-6, and upregulates mucin 4 gene expression in the human gastric epithelial cell line AGS, which may contribute to the promising beneficial gastroprotective effect of HM for human gastric prevention and treatment.

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