Endoplasmic Reticulum (ER) Stress Induces Sirtuin 1 (SIRT1) Expression via the PI3K-Akt-GSK3β Signaling Pathway and Promotes Hepatocellular Injury.

Sirtuin 1 (SIRT1), an NAD(+)-dependent histone deacetylase, plays crucial roles in various biological processes including longevity, stress response, and cell survival. Endoplasmic reticulum (ER) stress is caused by dysfunction of ER homeostasis and exacerbates various diseases including diabetes, fatty liver, and chronic obstructive pulmonary disease. Although several reports have shown that SIRT1 negatively regulates ER stress and ER stress-induced responses in vitro and in vivo, the effect of ER stress on SIRT1 is less explored.

CFTR-deficiency renders mice highly susceptible to cutaneous symptoms during mite infestation.

Pruritus, also known as itch, is a sensation that causes a desire to scratch. Prolonged scratching exacerbates skin lesions in several skin diseases such as atopic dermatitis. Here, we identify the cystic fibrosis transmembrane conductance regulator (CFTR/Cftr), an integral membrane protein that mediates transepithelial chloride transport, as a determinant factor in mice for the susceptibility to several cutaneous symptoms during mite infestation.

Endoplasmic reticulum stress increases the expression and function of toll-like receptor-2 in epithelial cells.

Endoplasmic reticulum (ER) stress is involved in a wide range of pathological conditions including neurodegenerative disorders, diabetes mellitus, atherosclerosis, inflammation, and infection. The ability of ER stress to induce an inflammatory response is considered to play a role in the pathogenesis of these diseases. However, its role in regulating the gene expression and function of toll-like receptors (TLRs), host defense receptors that recognize invading pathogens, remains unknown.

Curcumin decreases toll-like receptor-2 gene expression and function in human monocytes and neutrophils.

Toll-like receptor-2 (TLR2) is a pattern recognition receptor that senses many types of bacterial components and activates signaling pathways that induce inflammatory cytokines. A hyperresponsiveness to pathogens caused by increased expression of TLR2 triggers exaggeration of some inflammatory diseases. Here, we showed that curcumin, a well-known anti-inflammatory agent derived from the curry spice turmeric, inhibits TLR2 expression in various TLR2-expressing innate immune cell lines such as monocytic THP-1 cells, neutrophilic-differentiated HL-60 cells.

DNA demethylation-dependent enhancement of toll-like receptor-2 gene expression in cystic fibrosis epithelial cells involves SP1-activated transcription.

Background: The clinical course of cystic fibrosis (CF) is characterized by recurrent pulmonary infections and chronic inflammation. We have recently shown that decreased methylation of the toll-like receptor-2 (TLR2) promoter leads to an apparent CF-related up-regulation of TLR2. This up-regulation could be responsible, in part, for the CF-associated enhanced proinflammatory responses to various bacterial products in epithelial cells.

Increased responsiveness to TLR2 and TLR4 ligands during dimethylsulfoxide-induced neutrophil-like differentiation of HL-60 myeloid leukemia cells.

Neutrophils express functional toll-like receptor2 (TLR2) and 4 (TLR4) that are crucial for the production of inflammatory cytokines. Here, we show that dimethylsulfoxide-induced neutrophil-like differentiation of promyelocytic HL-60 cells (dHL-60) results in cells that respond to TLR2 and TLR4 ligands similarly to primary neutrophils. Consistent with the increased responsiveness of the cells to TLR2 ligand, the TLR2 gene was strongly up-regulated in dHL-60 cells.