Identification of IFN-γ-Producing Cells in IL-12/IL-18-Treated Mice

Otani, Takeshi; Nakamura, Shuji; Toki, M.; Motoda, Ryuichi; Kurimoto, Masashi; Orita, Kunzo

doi:10.1006/cimm.1999.1589

Cited by 77 publications

(63 citation statements)

References 26 publications

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“…NKT cell subpopulations may be double-negative, single-positive or double-positive with regards to CD4 and CD8 molecule expression [4,6,[7][8][9]. Recently, the involvement of NKT cells in modulating immune responses to various antigens has been implicated [7,[10][11][12][13][14][15][16][17][18][19]. They have been found to be essential in tumor rejection as well as in the prevention of autoimmune diseases, such as multiple sclerosis and chronic inflammatory demyelinating polyneuropathy [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

“…The mechanism underlying the initiation and development of allergic responses remains unclear. Due to the fact that NKT cells are capable of rapidly secreting key immunoregulatory cytokines such as IL-4 and IFN-+ [10,11], they are likely to play a role in modulating allergic diseases. However, comprehensive studies are lacking regarding the role of NKT cells and CD1 molecules in allergic responses especially in asthmatic reactions.…”

Section: Introductionmentioning

confidence: 99%

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Natural killer T cells contribute to airway eosinophilic inflammation induced by ragweed through enhanced IL‐4 and eotaxin production

et al. 2004

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Although NKT cells have been found to be capable of modulating immune responses in several model systems, the role of NKT cells in allergy remains unclear. Using CD1 gene knockout (KO) mice, which lack NKT cells, we examined the function of NKT cells in the development of allergic inflammation induced by a common airborne human allergen, ragweed. The data showed that airway eosinophilia and mucus overproduction induced by ragweed were significantly reduced in CD1 KO mice, which was correlated with significantly lower allergendriven IL-4 production and lower eotaxin responses in the airways of CD1 KO mice. Moreover, both ragweed-specific and total serum IgE levels in CD1 KO mice were significantly lower than those in control BALB/c mice. The reduced allergic reaction in CD1 KO mice is not due to intrinsic deficiency because they showed normal levels of immune cells and function. In addition, in vivo stimulation of NKT cells using their natural ligand, § -galactosylceramide, enhanced ragweed-induced airway eosinophilia, IL-4, and eotaxin production in control, but not CD1 KO mice. These data provide in vivo evidence for the involvement of NKT cells in the allergic mechanisms responsible for allergen-driven cytokine and chemokine production and airway inflammation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Natural killer T cells contribute to airway eosinophilic inflammation induced by ragweed through enhanced IL‐4 and eotaxin production

et al. 2004

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“…48 The ELISA results showed that the mice from rClone30-IL-12-IL-2 treatment group induced more IFN-g and IP-10 released, both of these molecules have been shown to be antiangiogenestic, which might be another important factor for resulting in inhibition of tumor growth. [25][26][27][28] The high expression level of the inserted genes within tumor and negligible in serum highlight the safety and efficiency of NDV serve as a vector for delivering human IL-12 and IL-2 into tumor cells in the future application. At the end of this study, virus-treated mice were rechallenged with the same tumor cells, and results showed that viral-treated mice were efficiently protected from rechallenged.…”

Section: Discussionmentioning

confidence: 99%

“…25,26 Extensive research suggested that IL-12 promotes an effective destruction of cancer cells by inducing proliferation of NK cells and T cells and production of IFN-g, and IL-12 enhances the generation and activity of cytotoxic T lymphocytes (CTLs) through activation of STAT4. [27][28][29][30] It is important to note that IFN-g is able to induce a powerful protection against the development of tumors by inducing the production of interferon-g-induced protein 10 (IP-10) and monokine induced by gamma-interferon (MIG), which promote antiangiogenic activity. In addition, several other mechanisms of IL-12 strongly contribute to antitumor activities.…”

Section: Introductionmentioning

confidence: 99%

Recombinant Newcastle Disease Virus Encoding IL-12 and/or IL-2 as Potential Candidate for Hepatoma Carcinoma Therapy

Ren

Tian

Liu

et al. 2016

Technol Cancer Res Treat

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Interleukins as immunomodulators are promising therapeutic agents for cancer therapy. Previous studies showed that there was an improved antitumor immunity in tumor-bearing mice using recombinant Newcastle disease virus carrying for interleukin-2. Interleukin-12 is a promising antitumor cytokine too. So we investigated and compared the antitumor effect of genetically engineered Newcastle disease virus strains expressing both interleukin-12 and/or interleukin-2 (rClone30-interleukin-2, rClone30-interleukin-12, and rClone30-interleukin-12-interleukin-2). In vitro studies showed that rClone30s could efficiently infect tumor cells and express interleukin-12 and/or interleukin-2. 3-(4,5-Dimethylthiazol-2-y)-2,5-diphenyl-tetrazolium bromide results showed rClone30s possessed strong cytotoxic activities against multiple tumor cell lines (U251, HepG2, A549, and Hela). Animal studies showed that rClone30-interleukin-12-interleukin-2 was more effective in inhibition of murine hepatoma carcinoma tumors, with the mean tumor volume (day 14) of 141.70 mm 3 comparing 165.67 mm 3 of rClone30-interleukin-12 group, 210.47 mm 3 of rClone30-interleukin-2 group, 574.70 mm 3 of rClone30 group, and 1206.83 mm 3 of phosphate-buffered saline group. Moreover, the rClone30-interleukin-12-interleukin-2 treated mice secreted more interferon g (333.518 pg/mL) and its downstream cytokine interferon-g induced protein 10 (16.006 pg/mL) in tumor than the rClone30-interleukin-12 group (interferon g: 257.548 pg/mL; interferon-g induced protein 10: 13.601 pg/mL), rClone30-interleukin2 group (interferon g: 124.601 pg/mL; interferon-g induced protein 10: 9.779 pg/mL), or rClone30 group (interferon g: 48.630 pg/mL; interferon-g induced protein 10:1.650 pg/mL). For the survival study, rClone30-interleukin12-interleukin2 increased the survival rate (12 of 16) of the tumor-bearing mice versus 11 of 16 in rClone30-interleukin-12 group, 10 of 16 in rClone30-interleukin-2 group, 7 of 16 in Clone30 group, and 0/16 in phosphate-buffered saline group, respectively. To determine whether the mice treated with recombinant virus developed protective immune response, the mice were rechallenged with the same tumor cells. The results showed that viral-treated mice were significantly protected from rechallenge. These results suggest that expressing both interleukin-2 and/or interleukin-12 could be ideal approaches to enhance the antitumor ability of Newcastle disease virus, and rClone30-interleukin-12-interleukin-2 is slightly superior over rClone30-interleukin-12 and rClone30-interleukin-2 alone.

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“…Studies have reported that IL-12 as a cytokine has antitumor therapeutic activities, and it has been shown to inhibit tumorigenesis and induce regression of established tumors. IL-12 promotes the effective destruction of cancer cells by inducing proliferation of NK and T cells, and IL-12 enhances the generation and activity of cytotoxic T lymphocytes (CTLs) (18,19). In addition, several other mechanisms of IL-12 strongly contribute to antitumor activities (20,21), and the antitumor activity of IL-12 can be improved by its combination with various therapeutics (22,23).…”

Section: Introductionmentioning

confidence: 99%

HBx-induced miR-21 suppresses cell apoptosis in hepatocellular carcinoma by targeting interleukin-12

Ding

Wang

et al. 2016

Oncology Reports

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Abstract. Hepatitis B virus (HBV) X protein (HBx) plays a key role in the initiation and progression of HBV infection-induced hepatocellular carcinoma (HCC). Oncogenic microRNA-21 (miR-21) can be modulated by HBx protein in HCC. However, critical regulator genes in the pathway of HBx-induced miR-21 in HCC remain unclear. This study aimed to investigate the role of HBx-induced miR-21 in the apoptosis of HCC cells. In the study, interleukin-12 (IL-12) was demonstrated as a direct target of miR-21 by dual-luciferase report assay, and miR-21 was highly expressed in HCC cells (HepG2 and HepG2 2.2.15) compared to L02 cells, but IL-12 was weakly expressed as detected by real-time quantitative PCR (RT-qPCR). Furthermore, miR-21 mimics, inhibitor, HBx-targeted siRNA, and the HBx overexpression vector (pHBx) were used to observe the regulatory effects of HBx-induced miR-21 via IL-12, and cell apoptosis was assessed. The results showed that overexpression of HBx resulted in the inhibition of IL-12. A high level of miR-21 resulted in a significant increase in proliferation and a decrease in IL-12 expression. Inhibition of miR-21 resulted in a significant increase in apoptosis and increased IL-12 expression. The results suggest that HCC cell apoptosis was suppressed at least partially through HBx-induced miR-21 by targeting IL-12.

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Identification of IFN-γ-Producing Cells in IL-12/IL-18-Treated Mice

Cited by 77 publications

References 26 publications

Natural killer T cells contribute to airway eosinophilic inflammation induced by ragweed through enhanced IL‐4 and eotaxin production

Natural killer T cells contribute to airway eosinophilic inflammation induced by ragweed through enhanced IL‐4 and eotaxin production

Recombinant Newcastle Disease Virus Encoding IL-12 and/or IL-2 as Potential Candidate for Hepatoma Carcinoma Therapy

HBx-induced miR-21 suppresses cell apoptosis in hepatocellular carcinoma by targeting interleukin-12

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