The novel cytokine interferon-gamma-inducing factor (IGIF) augments natural killer (NK) cell activity in cultures of human peripheral blood mononuclear cells (PBMC), similarly to the structurally unrelated cytokine interleukin (IL)-12. IGIF has been found to enhance the production of interferon-gamma (IFN-gamma) and granulocyte/macrophage colony-stimulating factor (GM-CSF) while inhibiting the production of IL-10 in concanavalin A (Con A)-stimulated PBMC. In this study, when anti-CD3 monoclonal antibody (mAb)-stimulated human enriched T cells were exposed to IGIF, the cytokine dose-dependently enhanced the proliferation of the cells and this could be completely inhibited by a neutralizing antibody against IL-2 at lower concentrations of IGIF. Neutralizing antibody against IFN-gamma had only insignificant inhibitory effects on T cell proliferation at higher concentrations of IGIF. Enzyme-linked immunosorbent assays (ELISA) revealed that, like PBMC, T cells exposed to IGIF produced large amounts of IFN-gamma; however, changes in the production of IL-4 and IL-10 were minimal. IGIF, but not IL-12, significantly enhanced IL-2 and GM-CSF production in T cell cultures, as determined by CTLL-2 bioassay and ELISA, respectively; however, both IGIF and IL-12 enhanced IFN-gamma production by the T cells. When T cells were exposed to a combination of IGIF and IL-12, a synergistic effect was observed on the production of IFN-gamma, but not on production of IL-2 and GM-CSF. In conclusion, IGIF enhances T cell proliferation apparently through an IL-2-dependent pathway and enhances Th1 cytokine production in vitro and exhibits synergism when combined with IL-12 in terms of enhanced IFN-gamma production but not IL-2 and GM-CSF production. Based on structural and functional differences from any known cytokines, it was recently proposed that this cytokine be designated interleukin-18.
Administration of monoclonal anti-CD3 antibody to mice treated with Propionibacterium acnes induced secretion of a high level of gamma interferon (IFN-␥) into the circulation system, while it induced no significant release in untreated mice. In order to analyze this high-level induction of IFN-␥ in these bacterium-treated mice, we investigated the factors that might be involved. An activity that induces IFN-␥ in T cells was observed in the liver extracts of mice treated with P. acnes and subsequently challenged with lipopolysaccharide. Here, we purified an IFN-␥-inducing factor from the liver extract to homogeneity and characterized it. Its molecular mass was 18 to 19 kDa, and its pI was 4.9. The amino acid sequence of the NH 2-terminal portion was determined and shown to have no similarities to any protein in the EMBL, GenBank, and PIR data bases. The same molecule was also demonstrated in the serum factor that was previously reported to have an IFN-␥inducing activity and to have an apparent molecular mass of 75 kDa. Moreover, the activity of this serum factor was recovered in the fraction containing the 18-to 19-kDa protein under reducing conditions and was shown to have the same NH 2-terminal amino acid sequence as that of the factor from the liver extract. In addition to the ability to induce IFN-␥, this protein augmented T-cell proliferation and NK activity in the spleen cells. Thus, several of its biological activities were apparently similar to those of interleukin-12. These results indicated that this novel protein, which exhibited marked costimulatory activity on IFN-␥ production in vitro, was elevated in vivo in response to P. acnes treatment. This factor, probably released from the producing cells by lipopolysaccharide stimuli, may be involved in the high-level induction of IFN-␥ in the P. acnes-treated mice. Recently CD4 ϩ T (Th) cells were divided into distinct subsets according to the profiles of cytokine production (15, 22, 23, 25). This will help our understanding of the regulatory mechanism of immune responses caused by infections with a variety of pathogens. Accessory cells or cytokines produced in response to the initial contact with antigens were shown to exhibit important functions in the development of these cells, depending on the antigenic characteristics. Cells of the Th2 subset are thought to require interleukin-1 (IL-1) or IL-4 for their development (6, 9, 11, 12, 24), and it is shown that IL-12 induces the differentiation of Th1 cells from uncommitted T cells (7, 13, 21). Gamma interferon (IFN-␥), which is produced by activated CD4 ϩ T (Th1), CD8 ϩ T, or NK cells, has been demonstrated to play important roles in cell-mediated immunity. Each of these producer cells may be regulated in the same or different manners, when stimulated. IL-2 was shown to induce IFN-␥ production in NK cells (3, 8), and IL-12 was demonstrated to be involved in IFN-␥ induction in CD4 ϩ T cells or NK cells (7, 13, 21). However, the detailed mechanisms underlying IFN-␥ production as well as the mechanism of devel...
Trehalose is a disaccharide that attracts much attention as a stress protectant. In this study, we investigated the mechanism of the antioxidant function of trehalose. The spin-lattice relaxation times (T(1)) of (1)H and (13)C NMR spectra were measured to investigate the interaction between trehalose and unsaturated fatty acid (UFA). We selected several kinds of UFA that differ in the number of double bonds and in their configurations (cis or trans). Several other disaccharides (sucrose, maltose, neotrehalose, maltitol, and sorbitol) were also analyzed by NMR. The T(1) values for the (1)H and (13)C signals assigned to the olefin double bonds in UFA decrease with increasing concentration of trehalose and the changes reaches plateaus at integer ratios of trehalose to UFA. The characteristic T(1) change is observed only for the combination of trehalose and UFA with cis double bond(s). On the other hand, from the (13)C-T(1) measurements for trehalose, the T(1) values of the C-3 (C-3') and C-6' (C-6) are found to change remarkably by addition of UFA. (1)H[bond](1)H NOESY measurements provide direct evidence for complexation of trehalose with linoleic acid. These results indicate that one trehalose molecule stoichiometrically interacts with one cis-olefin double bond of UFA. Computer modeling study indicates that trehalose forms a stable complex with an olefin double bond through OH...pi and CH...O types of hydrogen bonding. Furthermore, a significant increase in the activation energy is found for hydrogen abstraction reaction from the methylene group located between the double bonds that are both interacting with the trehalose molecules. Therefore, trehalose has a significant depression effect on the oxidation of UFA through the weak interaction with the double bond(s). This is the first study to elucidate the antioxidant function of trehalose.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.