Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Q: Context: SIRT3 is an important regulator in cell metabolism, and recent studies have shown that it may be involved in the pharmacological effects of metformin. However, the molecular mechanisms underlying this process are unclear.', 'The effects of SIRT3 on the regulation of oxidative stress and insulin resistance in skeletal muscle were evaluated in vitro. Differentiated L6 skeletal muscle cells were treated with 750 mol/L palmitic acid to induce insulin resistance. SIRT3 was knocked down and overexpressed in L6 cells. SIRT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) p65, c-Jun N-terminal kinase 1 (JNK1), and superoxide dismutase 2 (SOD2) were evaluated by Western blotting.', 'Over expression of SIRT3 increased glucose uptake and decreased ROS production in L6-IR cells as well as in L6 cells. Knock-down of SIRT3 induced increased production of ROS while decreased glucose uptake in both L6 and L6-IR cells, and these effects were reversed by N-acetyl-L-cysteine (NAC). Metformin increased the expression of SIRT3 (1.5-fold) and SOD2 (2-fold) while down regulating NF-B p65 (1.5-fold) and JNK1 (1.5-fold). Knockdown of SIRT3 (P < 0.05) reversed the metformin-induced decreases in NF-B p65 and JNK1 and the metformin-induced increase in SOD2 (P < 0.05).
Answer: Upregulated SIRT3 is involved in the pharmacological mechanism by which metformin promotes glucose uptake. Additionally, SIRT3 may function as an important regulator of oxidative stress and a new alternative approach for targeting insulin resistance-related diseases.

A: Does metformin ameliorate insulin resistance in L6 rat skeletal muscle cells through upregulation of SIRT3?
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Q: Context: Expression of CINCs was regulated differentially in lipopolysaccharide-stimulated rat macrophages. We examined whether the expression of CINCs in lipopolysaccharide-stimulated rat macrophages is similarly inhibited by anti-inflammatory drugs.', 'Rat peritoneal macrophages were stimulated by lipopolysaccharide in the presence of anti-inflammatory steroids (dexamethasone, prednisolone and hydrocortisone) or non-steroidal anti-inflammatory drugs (indomethacin and piroxicam). The production and mRNA expression of three types of CINCs were measured using enzyme-linked immunosorbent assay and northern hybridization.', 'Anti-inflammatory steroids; dexamethasone, prednisolone and hydrocortisone, dose-dependently inhibited the production of CINC-1, -2 and -3, whose inhibitory patterns were similar to each other. Furthermore mRNA expression of each CINC was inhibited by dexamethasone in a dose-dependent manner. In contrast, non-steroidal anti-inflammatory drugs, indomethacin and piroxicam were without effect. Expression of each CINC was regulated differently; the production of CINC-1 reached a maximum at 12 h and then slightly decreased after lipopolysaccharide stimulation, whereas that of CINC-2 and CINC-3 increased up to 24 h. Dexamethasone inhibited the CINCs production and mRNA expression at 9 h after lipopolysaccharide stimulation.
Answer: These results indicate no difference among CINC-1, -2 and -3 in the inhibition of production and mRNA expression of CINCs by anti-inflammatory steroids, although lipopolysaccharide differentially induces expression of each CINC expression in culture of rat macrophages.

A: Is the expression of three types of CINCs by lipopolysaccharide-stimulated rat macrophages inhibited similarly by anti-inflammatory steroids?
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Q: Context: Chronic ethanol (EtOH) has been shown to augment tumor necrosis factor (TNF)-alpha production, and this has been associated with EtOH-induced liver injury. We have recently described a chronic in vitro cell culture model where chronic ethanol exposure results in significantly augmented TNF production in Mono Mac 6 cells, a human monocytic cell line. This enhanced TNF production was redox regulated and associated with increased levels of TNF messenger RNA (mRNA) as well as increased processing of TNF by TNF converting enzyme (TACE), the enzymatic activity of which is regulated by the cellular redox state. We hypothesized that chronic ethanol through oxidative stress activates TACE-mediated ectodomain shedding of the preformed substrates p75 and p55 TNF receptors in Mono Mac 6 cells and L-selectin in Jurkat T cells.', 'Mono Mac 6 or Jurkat T cells were treated with EtOH (0, 50, or 100 mM) for 4 to 6 days. Shedding of p75 and p55 TNF receptors (Mono Mac 6 cells) or L-selectin (Jurkat T cells) was induced by stimulation with lipopolysaccharide and phorbol myristate acetate for Mono Mac 6 cells and PMA alone for Jurkat T cells. Shedding was assessed by enzyme-linked immunosorbent assay for shed molecules in the cell supernatant as well as the cell-associated proteins recovered from cell pellets. Steady-state mRNA levels for p75 TNF receptor and L-selectin were determined by ribonuclease protection assay. Cell surface L-selectin and TACE were measured by flow cytometry, and cell associated p55 and p75 TNF receptors were measured by enzyme-linked immunosorbent assay.', 'Chronic EtOH exposure for 6 days resulted in a significant dose-dependent increase in shedding of p75 and p55 TNF receptors from Mono Mac 6 cells and L-selectin from Jurkat T-cells. The enhanced shedding was correlated with an alcohol-induced increase in mRNA levels and cell surface protein levels for these TACE substrates. Although chronic EtOH exposure increased the total amount of p75 and p55 TNF receptor and L-selectin shed into the media, the efficiency of shedding was suppressed by EtOH. In the case of Mono Mac 6 cells, the EtOH exposure increased superoxide production. Inhibition of nicotinamide adenine dinucleotide phosphate (reduced form) oxidase and hydrogen peroxide partially prevented the increased production of p75 TNF receptor in these cells.
Answer: These results suggest that chronic EtOH up-regulates p75 and p55 TNF receptors on monocytes and L-selectin on T-cells. However, the TACE-mediated shedding efficiency of these substrates may be inhibited in the presence of EtOH. These results may have implications in monocyte signaling and T-cell trafficking, which may, in part, contribute to immune dysregulation associated with chronic ethanol.

A:
Does chronic ethanol enhance ectodomain shedding in T cells and monocytes?
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