Correlation of serum toll like receptor 9 and trace elements with lipid peroxidation in the patients of breast diseases

Park

et al. 2016

Sci Rep

Recently, a possible link between toll-like receptor 7 (TLR7) and liver disease was suggested, although it was limited to fibrosis. Based on this report, we investigated whether TLR7 has a pivotal role in non-alcoholic fatty liver disease (NAFLD). The TLR7 signaling pathway, which is activated by imiquimod (TLR7 ligand) naturally, induced autophagy and released insulin-like growth factor 1 (IGF-1) into medium from hepatocytes. Lipid accumulation induced by unsaturated fatty acid (UFA; arachidonic acid:oleic acid = 1:1) in hepatocytes, was attenuated in TLR7 and autophagy activation. Interestingly, TLR7 activation attenuated UFA-induced lipid peroxidation products, such as malondialdehyde (MDA) and 4-Hydroxy-2-Nonenal (4-HNE). To clarify a possible pathway between TLR7 and lipid peroxidation, we treated hepatocytes with MDA and 4-HNE. MDA and 4-HNE induced 2-folds lipid accumulation in UFA-treated hepatocytes via blockade of the TLR7 signaling pathway’s IGF-1 release compared to only UFA-treated hepatocytes. In vivo experiments carried out with TLR7 knockout mice produced results consistent with in vitro experiments. In conclusion, TLR7 prevents progression of NAFLD via induced autophagy and released IGF-1 from liver. These findings suggest a new therapeutic strategy for the treatment of NAFLD.

“…A few studies reported an association between lipid peroxidation products and TLRs343536. However, no studies have connected TLR7 and lipid peroxidation products.…”

Section: Resultsmentioning

confidence: 99%

Toll-like receptor 7 affects the pathogenesis of non-alcoholic fatty liver disease

Park

et al. 2016

Sci Rep

“…A recent research showed that HNE increased the growth of breast cancer cells and promoted their angiogenesis and invasion [112]. Elevated levels of MDA were observed in plasma and blood serum of patients with breast, lung, ovarian, thyroid, and oral cancer, and precancer states [113–122]. The MDA levels in patients with lung cancer correlated with the cancer stage [123].…”

Section: Poducts Of Lipid Peroxidation As Common Markers Of Oxidativementioning

confidence: 99%

Mitochondrial dysfunction and oxidative stress in aging and cancer

et al. 2016

Aging and cancer are the most important issues to research. The population in the world is growing older, and the incidence of cancer increases with age. There is no doubt about the linkage between aging and cancer. However, the molecular mechanisms underlying this association are still unknown. Several lines of evidence suggest that the oxidative stress as a cause and/or consequence of the mitochondrial dysfunction is one of the main drivers of these processes. Increasing ROS levels and products of the oxidative stress, which occur in aging and age-related disorders, were also found in cancer. This review focuses on the similarities between ageing-associated and cancer-associated oxidative stress and mitochondrial dysfunction as their common phenotype.

“…59 As a family, TLRs are expressed by multiple immune cells, including macrophages, dendritic cells (DCs), B cells, and natural killer (NK) cells, as well as by non-immune cells including epithelial cells, fibroblasts and malignant cells. [60][61][62] Thus, besides controlling the activation, maturation and immunological functions of immune cells (notably cytokine secretion), [63][64][65][66][67][68][69] TLR signaling can influence tumor metabolism, proliferation and dissemination.- 60,62,[70][71][72][73][74][75] Several TLR ligands demonstrated potential therapeutic efficacy against malignant disorders. 70,76 Imiquimod, also called Aldara® (imiquimod 5% cream as commercialized by 3M Pharmaceuticals) or R-837, is a TLR7 agonist that is approved by the US Food and Drug Administration (FDA) for the treatment of actinic keratosis, external genital/perianal warts (condylomata acuminata), and superficial basal cell carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Trial Watch: Toll-like receptor agonists in cancer immunotherapy

et al. 2018

Toll-like receptor (TLR) agonists demonstrate therapeutic promise as immunological adjuvants for anticancer immunotherapy. To date, three TLR agonists have been approved by US regulatory agencies for use in cancer patients. Additionally, the potential of hitherto experimental TLR ligands to mediate clinically useful immunostimulatory effects has been extensively investigated over the past few years. Here, we summarize recent preclinical and clinical advances in the development of TLR agonists for cancer therapy.