The antioxidant response element (ARE) is a transcriptional control element that mediates expression of a set of antioxidant proteins. NF-E2-related factor 2 (Nrf2) is a transcription factor that activates ARE-containing genes. In endothelial cells, the ARE-mediated genes are upregulated by atheroprotective laminar flow through a Nrf2-dependent mechanism. We tested the hypothesis that activation of ARE-regulated genes via adenovirus-mediated expression of Nrf2 may suppress redox-sensitive inflammatory gene expression. Expression of Nrf2 in human aortic endothelial cells (HAECs) resulted in a marked increase in ARE-driven transcriptional activity and protected HAECs from H2O2-mediated cytotoxicity. Nrf2 suppressed TNF-α-induced monocyte chemoattractant protein (MCP)-1 and VCAM-1 mRNA and protein expression in a dose-dependent manner and inhibited TNF-α-induced monocytic U937 cell adhesion to HAECs. Nrf2 also inhibited IL-1β-induced MCP-1 gene expression in human mesangial cells. Expression of Nrf2 inhibited TNF-α-induced activation of p38 MAP kinase. Furthermore, expression of a constitutively active form of MKK6 (an upstream kinase for p38 MAP kinase) partially reversed Nrf2-mediated inhibition of VCAM-1 expression, suggesting that p38 MAP kinase, at least in part, mediates Nrf2's anti-inflammatory action. In contrast, Nrf2 did not inhibit TNF-α-induced NF-κB activation. These data identify the Nrf2/ARE pathway as an endogenous atheroprotective system for antioxidant protection and suppression of redox-sensitive inflammatory genes, suggesting that targeting the Nrf2/ARE pathway may represent a novel therapeutic approach for the treatment of inflammatory diseases such as atherosclerosis.

We tested expectations that two desert shrubs would differ in germination and seedling relative growth rate (RGR) responses to Na and Ψ(s) stress. The study species, Chrysothamnus nauseosus ssp. consimilis and Sarcobatus vermiculatus (hereafter referred to by genus), differ in their distribution along salinity gradients, with Chrysothamnus inhabiting only less saline areas. In growth chamber studies, declining Ψ(s) (-0.82 to -2.71 MPa) inhibited germination of both species, and Chrysothamnus was less tolerant of Ψ(s) stress than Sarcobatus. Germination fell below 10% for Chrysothamnus at -1.64 MPa (NaCl and PEG), and for Sarcobatus at -2.4 MPa PEG. Neither species exhibited ion toxicity. There was substantial ion enhancement for Sarcobatus in lower Ψ(s), allowing for 40% germination in -2.71 MPa NaCl. For seedling RGR, species were not different at -0.29 or -0.82 MPa (0 and 100 mmol/L NaCl, respectively), but Chrysothamnus RGR declined substantially at -1.3 MPa (200 mmol/L NaCl). The greater stress tolerance of Sarcobatus was not associated with a lower RGR under nonsaline conditions. Species differences in seed and seedling Ψ(s) stress tolerance probably contribute to the restricted distribution of Chrysothamnus to less saline areas. The Na uptake of Sarcobatus seedlings enhances its ability to deal with declining Ψ(s) and establish in more saline areas.

These data suggest that sulforaphane may be useful as a therapeutic agent for the treatment of inflammatory diseases.

CD4؉ T-cell dysfunction highlighted by defects within the intracellular signaling cascade and cell cycle has long been characterized as a direct and/or indirect consequence of human immunodeficiency virus (

Human immunodeficiency virus infection in humans and simian immunodeficiency virus (SIV) infection in rhesus macaques (RM) leads to a generalized loss of immune responses involving perturbations in T-