Galectin-9 Protein Expression in Endothelial Cells Is Positively Regulated by Histone Deacetylase 3

Galectin-9 expression in endothelial cells can be induced in response to inflammation. However, the mechanism of its expression remains unclear. In this study, we found that interferon-γ (IFN-γ) induced galectin-9 expression in human endothelial cells in a time-dependent manner, which coincided with the activation of histone deacetylase (HDAC). When endothelial cells were treated with the HDAC3 inhibitor, apicidin, or shRNA-HDAC3 knockdown, IFN-γ-induced galectin-9 expression was abolished. Overexpression of HDAC3 induced the interaction between phosphoinositol 3-kinase (PI3K) and IFN response factor 3 (IRF3), leading to IRF3 phosphorylation, nuclear translocation, and galectin-9 expression. HDAC3 functioned as a scaffold protein for PI3K/IRF3 interaction. In addition to galectin-9 expression, IFN-γ also induced galectin-9 location onto plasma membrane, which was HDAC3-independent. Importantly, HDAC3 was essential for the constitutive transcription of PI3K and IRF3, which might be responsible for the basal level of galectin-9 expression. The phosphorylation of IRF3 was essential for galectin-9 expression. This study provides new evidence that HDAC3 regulates galectin-9 expression in endothelial cells via interaction with PI3K-IRF3 signal pathway

Assessment of Heavy Metal Contamination and Health Risk Associated with Cultivated Vegetables along Dhaka-Mymensingh Highway, Bangladesh

The purpose of this research work is to evaluate the degree of eight heavy metals (Fe, Mn, Cu, Zn, Cd, Pb, Cr, and Ni) contamination and health risks of three regularly consumed vegetables (papaya, bottle gourd, and esculent) near one of Bangladesh’s busiest roadways, the Dhaka-Mymensingh highway. The heavy metal concentrations in 45 vegetable samples were analyzed using an atomic absorption spectrometer (AAS). These samples were collected from five different sampling sites based on various land use patterns adjacent to the highway. The average concentrations (mg/kg) of Cu, Fe, Mn, Zn, Cr, and Ni were found to be 9.86, 246.8, 16.9, 28.0, 9.02, and 2.02, respectively, for papaya; 14.9, 281.2, 387.6, 49.0, 10.1, and 2.92, respectively, for bottle gourd; and 17.6, 183.4, 107.2, 80.7, 7.98, and 2.34, respectively, for esculent. The mean concentrations of Cr, Zn, and Mn in papaya, bottle gourd, and esculent were higher than the acceptable limit. Correlation analysis revealed a significant positive correlation between Fe-Cu, Zn-Fe, Cu-Fe, and Fe-Zn in papaya; Cu-Zn, Fe-Cr, Zn-Ni, and Cr-Fe in bottle gourd; and Mn-Cr, Mn-Ni, Mn-Fe, and Cr-Ni in esculent, thereby indicating their common anthropogenic sources like agricultural activities, waste from the commercial area, filling station, and vehicular emissions. Health risk assessment through target hazard quotient (THQ) revealed the highest THQ of 9.52 for Cr in bottle gourd, which poses a high non-carcinogenic health risk to the localities upon the intake of these contaminated vegetables. Target cancer risk (TCR) was found to be highest for Cr in papaya (0.013) and bottle gourd (0.014). TCR trends were found for Cr in the following order: bottle gourd \u3e esculent \u3e papaya. This study contributed the greatest concern for both carcinogenic and non-carcinogenic health impacts through ingesting contaminated vegetables

TRPV1 deletion enhances local inflammation and accelerates the onset of Systemic Inflammatory Response Syndrome

Abstract The transient receptor potential vanilloid 1 (TRPV1) is primarily localized to sensory nerve fibers and is associated with the stimulation of pain and inflammation. TRPV1 knockout (TRPV1KO) mice show enhanced LPS-induced sepsis compared with wild type (WT). This implies that TRPV1 may have a key modulatory role in increasing the beneficial and reducing the harmful components in sepsis. We investigated immune and inflammatory mechanisms in a cecal ligation and puncture (CLP) model of sepsis over 24 h. CLP TRPV1KO mice exhibited significant hypothermia, hypotension, and organ dysfunction compared with CLP WT mice. Analysis of the inflammatory responses at the site of initial infection (peritoneal cavity) revealed that CLP TRPV1KO mice exhibited: 1) decreased mononuclear cell integrity associated with apoptosis, 2) decreased macrophage tachykinin NK1-dependent phagocytosis, 3) substantially decreased levels of nitrite (indicative of NO) and reactive oxygen species, 4) increased cytokine levels, and 5) decreased bacteria clearance when compared with CLP WT mice. Therefore, TRPV1 deletion is associated with impaired macrophage-associated defense mechanisms. Thus, TRPV1 acts to protect against the damaging impact of sepsis and may influence the transition from local to a systemic inflammatory state.</jats:p

XBP1 mRNA splicing triggers an autophagic response in endothelial cells through BECLIN-1 transcriptional activation

Sustained activation of X-box-binding protein 1 (XBP1) results in endothelial cell (EC) apoptosis and atherosclerosis development. The present study provides evidence that XBP1 mRNA splicing triggered an autophagic response in ECs by inducing autophagic vesicle formation and markers of autophagy BECLIN-1 and microtubule-associated protein 1 light chain 3β (LC3-βII). Endostatin activated autophagic gene expression through XBP1 mRNA splicing in an inositol-requiring enzyme 1α (IRE1α)-dependent manner. Knockdown of XBP1 or IRE1α by shRNA in ECs ablated endostatin-induced autophagosome formation. Importantly, data from arterial vessels from XBP1 EC conditional knock-out (XBP1eko) mice demonstrated that XBP1 deficiency in ECs reduced the basal level of LC3β expression and ablated response to endostatin. Chromatin immunoprecipitation assays further revealed that the spliced XBP1 isoform bound directly to the BECLIN-1 promoter at the region from nt −537 to −755. BECLIN-1 deficiency in ECs abolished the XBP1-induced autophagy response, whereas spliced XBP1 did not induce transcriptional activation of a truncated BECLIN-1 promoter. These results suggest that XBP1 mRNA splicing triggers an autophagic signal pathway through transcriptional regulation of BECLIN-1