Cellular Mechanisms in<i>In Vivo</i>Production of Gamma Interferon Induced by Lipopolysaccharide in Mice Infected with<i>Mycobacterium bovis</i>BCG

Wada, Masaaki; Okamura, Haruki; Nagata, Kumiko; Shimoyama, Takashi; Kawade, Yoshimi

doi:10.1089/jir.1985.5.431

Cited by 12 publications

(9 citation statements)

References 26 publications

(2 reference statements)

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“…Recently, it was demonstrated that IFN-y is involved in the LPS-induced inflammatory response (4,8), and previ-ously, we found that LPS stimulated production of IFN--y and IFN-at/, in BCG-infected mice or in mice treated with heat-killed Propionibacterium acnes (20,28). Because these bacteria do not contain LPS, IFN--y induction by LPS did not appear to be due to an antigen-specific stimulus but rather to the ability of LPS to cause inflammation.…”

Section: Discussionmentioning

confidence: 71%

“…Previously, we found that high titers of IFN--y were released into the circulatory system of bacteria-treated mice upon challenge with endotoxin (lipopolysaccharide [LPS]) (20,28). LPS was also shown to induce IFN-y in lymphoid cells with the help of 14,21), and recently the involvement of IFN-y in LPS-induced inflammatory reactions was suggested (4,8).…”

mentioning

confidence: 99%

“…Because accessory cells were required for IFN--y induction by LPS and it seemed unlikely that LPS directly stimulated the producer cells, we were prompted to search for a second soluble factor participating in the induction mechanism of IFN--y production by LPS in vivo. Since high titers of IFN--y induced by LPS in bacteriatreated mice seemed to appear in the later phase (20,28), such a factor would probably exist in the circulation before the appearance of IFN--y.…”

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confidence: 99%

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Endotoxin-induced serum factor that stimulates gamma interferon production

et al. 1989

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Serum from Mycobacterium bovis BCG-infected mice that had been challenged with lipopolysaccharide (LPS) exhibited a marked ability to induce gamma interferon (IFN-y) in cultures of spleen cells of normal mice in the presence of interleukin-2 (IL-2). The inducing activity became detectable in the circulatory system about 90 min after LPS challenge, disappeared at around 5 h, and was observable upon 640x dilution of the serum. Addition of monoclonal anti-IL-2 receptor antibody to the culture inhibited the induction by the serum. The activity induced high levels of IFN-y even in nylon wool-nonadherent cells, while concanavalin A failed to do so. Serum from uninfected mice challenged with LPS contained no such activity. The molecular weight of the active substance, estimated by gel filtration, was about 70,000. There were pronounced differences among mouse strains in the activities of the sera prepared, which paralleled the amounts of IFN-y produced in vivo. However, the levels of IFN-y produced in whole spleen cells and in nylon wool-nonadherent cells from mice of various strains were the same when stimulated with competent serum. These results indicate the existence of an unidentified factor that induces IFN-y in cooperation with IL-2 in macrophage-depleted splenocytes. They also suggest that IFN-,y production in vivo is not genetically controlled at the lymphocyte level but, rather, at the level of synthesis of the unknown factor.

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Section: Discussionmentioning

confidence: 71%

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confidence: 99%

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confidence: 99%

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Endotoxin-induced serum factor that stimulates gamma interferon production

et al. 1989

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“…In the previous studies, we showed that mitogens or antigens induced high levels of IFN-␥ production in mice pretreated with P. acnes or Mycobacterium bovis BCG while they did not in untreated mice (18,26). As shown in Fig.…”

Section: Changes In the Levels Of In Vivo Ifn-␥ Induction And Levels mentioning

confidence: 69%

A novel costimulatory factor for gamma interferon induction found in the livers of mice causes endotoxic shock

et al. 1995

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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...

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“…This serum contained IFN-a/1 but not IFN--y, which appeared about 2 h later. Although live BCG was available for pretreatment (22), killed P. acnes was employed for the present study because the latter grew more rapidly and the incubation period for pretreatment was much shorter (23,32).…”

Section: Methodsmentioning

confidence: 99%

Purification of a factor which provides a costimulatory signal for gamma interferon production

et al. 1993

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A protein factor which induces high levels of gamma interferon (IFN-y) in resting splenic nonadherent cells was isolated from the sera of mice with generalized inflammation caused by endotoxic shock. The factor was highly purified by ammonium sulfate precipitation followed by ion-exchange column chromatography on DEAE-Sepharose, molecular sieving on Ultrogel AcA 44, and hydrophobic column chromatography with phenyl-Sepharose. It was further purified to apparent homogeneity by polyacrylamide gel electrophoresis. It induced IFN-y production in a dose-dependent manner in the presence of interleukin-2, monoclonal anti-CD3 antibody (anti-CD3 MAb), or concanavalin A (ConA) in spleen cells deprived of plastic plate-and nylon wool-adherent cells. Anti-CD3 MAb induced the highest level of production of the three. The factor, interleukin-2, anti-CD3 MAb, or ConA alone induced a trace of or no detectable IFN-y in these cells. The factor also exhibited an accessory function during proliferation in these cells in the presence of a suboptimal dose of ConA. However, the factor failed to stimulate IFN-y production when staphylococcal enterotoxin A, a superantigenic T-cell mitogen, was employed. Treatment with pronase or heat abolished these activities. These studies confirm the existence of a soluble protein factor which is able to exhibit a novel accessory function in IFN-y production in resting T or natural killer cells. It will be of interest to compare this factor with the recently cloned human natural killer stimulatory factor (NKSF/IL-12).

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Cellular Mechanisms inIn VivoProduction of Gamma Interferon Induced by Lipopolysaccharide in Mice Infected withMycobacterium bovisBCG

Cited by 12 publications

References 26 publications

Endotoxin-induced serum factor that stimulates gamma interferon production

Endotoxin-induced serum factor that stimulates gamma interferon production

A novel costimulatory factor for gamma interferon induction found in the livers of mice causes endotoxic shock

Purification of a factor which provides a costimulatory signal for gamma interferon production

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