• Tuberculosis and Respiratory Diseases
• /
• v.47 no.2
• /
• pp.161-171
• /
• 1999

Background: Interleukin-12 (IL-12) can induce antitumor effects in vivo. This antitumor effect is associated with T cell infiltration but the effect of IL-12 on the steps of T cell migration into the tumor tissue has not been fully elucidated. This study focused on the effect of IL-12 on the tumor growth and the metastasis and on the expression of E-selectin, an adhesion molecule which is activated endothelial specific in its expression. In addition, we studied whether the expression of E-selectin is associated with the TNF-$\alpha$, a cytokine that its production is increased by IL-12 and has functions inducing a variety of adhesion molecules. Methods: Mice of C57BL/6 strain were injected with Lewis lung cancer cells followed by either IL-12, TNF-$\alpha$, or normal saline by intraperitoneal route. Twenty eight days after tumor cell inoculation, metastatic nodules of lung were enumerated and immunohistochemical staining of the subcutaneous tumors were performed with monoclonal antibodies to CD4, CD8, CD16, and E-selectin. In IL-12 treated mice, the subcutaneously implanted Lewis lung tumors were decreased in size and the metastases were also decreased in number compared to control mice. On tumor tissues, increased infiltration of CD4+, CD8+, and CD16+ cells were oberved in IL-12 treated mice compared to control mice. In control mice, E-selectin was absent on tumor vessels, but the expression of E-selectin was increased on tumor vessels of IL-12 treated mice. Administration of TNF-$\alpha$ increased not only the expression of E-selectin but also infiltrations of CD4+, CD8+, and CD16+ cells on tumor tissues. Conclusions: These results demonstrate that IL-12 inhibits tumor growth and metastases through infiltrations of inflammatory cells in mouse model of Lewis lung carcinoma and E-selectin may playa role in inflammatory cell recruitment on tumor tissue following IL-12 administration. Also, TNF-$\alpha$ may have a role as a mediator responsible for the IL-12 induced expression of E-selectin.

• IMMUNE NETWORK
• /
• v.9 no.3
• /
• pp.106-113
• /
• 2009

Background: We previously demonstrated remarkable differences in the expression of IL-8/CXCL8 in aortic tissues and vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) compared to VSMC from normotensive Wistar-Kyoto rats (WKY). In the present study, we investigated the direct effect of IL-8/CXCL8 on expression of 12-lipoxygenase (LO), a hypertensive modulator, in SHR VSMC. Methods: Cultured aortic VSMC from SHR and WKY were used. Expression of 12-LO mRNA was determined by real-time polymerase chain reaction. Phosphorlyation of ERK1/2 and production of 12-LO and angiotensin II subtype 1 ($AT_1$) receptor were assessed by Western blots. IL-8/CXCL8-stimulated DNA synthesis was determined by measuring incorporation of [$^3H$]-thymidine. And effect of IL-8/CXCL8 on vascular tone was determined by phenylephrine-induced contraction of thoracic aortic rings. Results: Treatment with IL-8/CXCL8 greatly increased 12-LO mRNA expression and protein production compared to treatment with angiotensin II. IL-8/CXCL8 also increased the expression of the $AT_1$ receptor. The increase in 12-LO induced by IL-8/CXCL8 was inhibited by treatment with an $AT_1$ receptor antagonist. The induction of 12-LO mRNA production and the proliferation of SHR VSMC by IL-8/CXCL8 was mediated by the ERK pathway. The proliferation of SHR VSMC and the vascular contraction in the thoracic aortic ring, both of which were induced by IL-8/CXCL8, were inhibited by baicalein, a 12-LO inhibitor. Conclusion: These results suggest that the potential role of IL-8/CXCL8 in hypertensive processes is likely mediated through the 12-LO pathway.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.10
• /
• pp.5747-5751
• /
• 2013

Golgi phosphoprotein 2 (GOLPH2) is a very important biomarker in a variety of diseases. Its biological function is not clear, particularly in gastric cancer. To investigate the role of GOLPH2 in human gastric cancer, and determine its effect on the Th1 lymphocyte response, its expression and that of IL-12A were measured by real-time PCR and immunohistochemistry. The relationship between GOLPH2 and IL-12A was analysed statistically. The effect of GOLPH2 on the Th1 lymphocyte response was investigated with an in vitro co-culture system. The results showed that in human gastric cancer, the expression of GOLPH2 was significantly higher and the expression of IL-12A was lower than in normal gastric mucosal tissues, and the expression levels of GOLPH2 and IL-12A were negatively correlated. In addition, obvious down-regulation of the Th1 response was observed when lymphocytes were co-cultured with gastric cancer SGC7901 cells over-expressing GOLPH2. GOLPH2 down-regulated the expression of IL-12A, and inhibited the expression of TNF-${\alpha}$ and IFN-${\gamma}$. The results indicated that GOLPH2 down-regulates the Th1 response via suppression of IL-12A in human gastric cancer, and this might provide a target for the prevention and treatment.

• Macromolecular Research
• /
• v.13 no.4
• /
• pp.293-296
• /
• 2005

Transferrin ($T_{f}$) has been used as a targeting ligand for delivering liposome/interleukin-12 (IL-12) pDNA complexes to cancer cells mostly due to the greater number of transferrin receptors ($T_{f}R$) found on tumor cells than on normal cells. $T_{f}$ was conjugated to liposomes via the reaction of MPB-PE with thiol groups of $T_{f}$ introduced by a heterobifunctional cross-linking agent, N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP). Four days after C26 inoculation when the tumor volume reached ${\sim}100mm^{3}$, tumor-bearing Balb/c mice were injected intravenously with $T_{f}-liposome/IL-12 pDNA$complexes twice a week for 3 weeks. Significant suppression of tumor growth was achieved in the group treated with the $T_{f}-liposome/IL-12 pDNA$ complexes, with a dose of $10{\mu}g$ of IL-12 pDNA showing the highest suppression effect among the tested doses. Similar results were obtained when the therapy was initiated one day after tumor inoculation, although in this case $30{\mu}g$ IL-12 pDNA/$T_{f}-liposome$ complexes showed a significant suppression of tumor growth between 19 and 23 days after tumor inoculation. This result indicates that the transferrin receptor-targeted liposomal system is an efficient delivery agent of therapeutic genes, such as IL-12, in mice and that its potential clinical use warrants further research investigation.

• Parasites, Hosts and Diseases
• /
• v.55 no.6
• /
• pp.613-622
• /
• 2017

IL-12 and IL-23 are closely related in structure, and have been shown to play crucial roles in regulation of immune responses. However, little is known about the regulation of these cytokines in T cells. Here, we investigated the roles of PI3K and MAPK pathways in IL-12 and IL-23 production in human Jurkat T cells in response to Toxoplasma gondii and LPS. IL-12 and IL-23 production was significantly increased in T cells after stimulation with T. gondii or LPS. T. gondii and LPS increased the phosphorylation of AKT, ERK1/2, p38 MAPK, and JNK1/2 in T cells from 10 min post-stimulation, and peaked at 30-60 min. Inhibition of the PI3K pathway reduced IL-12 and IL-23 production in T. gondii-infected cells, but increased in LPS-stimulated cells. IL-12 and IL-23 production was significantly reduced by ERK1/2 and p38 MAPK inhibitors in T. gondii- and LPS-stimulated cells, but not in cells treated with a JNK1/2 inhibitor. Collectively, IL-12 and IL-23 production was positively regulated by PI3K and JNK1/2 in T. gondii-infected Jurkat cells, but negatively regulated in LPS-stimulated cells. And ERK1/2 and p38 MAPK positively regulated IL-12 and IL-23 production in Jurkat T cells. These data indicate that T. gondii and LPS induced IL-12 and IL-23 production in Jurkat T cells through the regulation of the PI3K and MAPK pathways; however, the mechanism underlying the stimulation of IL-12 and IL-23 production by T. gondii in Jurkat T cells is different from that of LPS.

• Preventive Nutrition and Food Science
• /
• v.20 no.2
• /
• pp.83-87
• /
• 2015

Omega-3, a polyunsaturated fatty acid, is an essential fatty acid necessary for human health, and it protects against cardiovascular disease, inflammation, autoimmune diseases, and cancer. In the present study, we investigated the effects of omega-3-rich harp seal oil (HSO) on the production of nitric oxide (NO) and cytokines, such as tumor necrosis factor (TNF)-${\alpha}$, interleukin-(IL)-$1{\beta}$, IL-6, and IL-12/IL-23 (p40) in peritoneal macrophages of mice. The culture supernatants of murine macrophages exposed to lipopolysaccharide (LPS), HSO, or HSO+LPS were harvested to assay IL-$1{\beta}$, TNF-${\alpha}$, IL-6, and IL-12/IL-23 (p40) cytokines and NO. TNF-${\alpha}$, IL-$1{\beta}$, and IL-12/IL-23 (p40) levels, except IL-6, were lower in the culture supernatants of mouse peritoneal macrophages exposed to LPS plus HSO than those of the groups exposed to LPS alone. These observations demonstrate that omega-3-rich harp seal oil downregulates the production of the pro-inflammatory cytokines such as IL-$1{\beta}$, TNF-${\alpha}$, and IL-12/IL-23 (p40). These results suggest that HSO could be potentially used as a preventive agent or as an adjunct in anti-inflammatory therapy, if more research results were accumulated.

• Archives of Pharmacal Research
• /
• v.25 no.6
• /
• pp.954-963
• /
• 2002

Lectin-conjugated praecoxin A is a compound, which is combined Wheat Germ Agglutinin (WGA) Lectin with praecoxin A and also known to have an anti-tumor activity. In our lab, in order to investigate its immune reaction other than the anti-tumor activity ever known, we examined cytokines such as IL-6 and IL-12 through their mRNA expressions, which are generally secreted by macrophage both in vivo and in vitro. To analyze, we used RT-PCR for total RNAs of macrophages. As a result, we obtained that both in vitro and in vivo, lectin-conjugated praecoxin A showed an interesting increase on IL-6 and IL-12 even though it may be little hard to say the conjugated form is absolutely more effective than that of lectin or praecoxin A alone for immune response activities. Those results suggest that the conjugated form may give an additional opportunity in a future therapeutic use over its immuno activation properties.

• Clinical and Experimental Pediatrics
• /
• v.51 no.7
• /
• pp.754-759
• /
• 2008

Purpose : Abnormal activation patterns of Th1/Th2-cells have been suggested to increase the prevalence of allergic diseases. Prevention is regarded as an important corner stone in the management of allergic diseases. In this study, we have investigated the relationship between cord blood levels of IL-4, IL-10, and IL-12 in preterm newborns and the development of allergic respiratory diseases in infancy Methods : Forty-six preterm newborns born at the Ewha Womans University Mokdong Hospital between January 2003 and July 2005, were enrolled for this study, and consent was obtained to test their cord blood samples. Clinical history was obtained from the hospital records. Cord blood was obtained at birth and kept frozen until it was tested. The levels of IL-4, IL-10, and IL-12 were determined by enzyme-linked immunosorbent assay (ELISA). Results : All infants were followed-up for a median of $16.0months{\pm}13.2d$ (range, 12.0 to 36.0 months). Eighteen infants who developed wheezing showed lower cord blood levels of IL-12 ($366.60{\pm}140.40$ vs $435.09{\pm}91.20pg/mL$, P=0.009). Cord blood levels of IL-4 and IL-10 showed no significant difference between the two groups. Four newborns who later developed asthma, and infants with asthma showed lower IL-12 level in the cord blood than other groups. Conclusion : Lower concentration of cord blood levels of IL-12 in newborns who later developed wheezing and asthma suggested that they had abnormal activation patterns of Th1/Th2-cells at the time of birth, and cord blood IL-12 level can be used as a predictor of allergic respiratory diseases.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.18
• /
• pp.7869-7873
• /
• 2014

Interleukin-12 (IL-12) as an antitumor and interleukin-6 (IL-6) as an inflammatory cytokine, are immunomodulatory products that play important roles in responses in cancers and inflammation. We tested the association between two polymorphisms of IL-12(1188A>C; rs3212227) and IL-6 (-174 C>G) and the risk of bladder cancer in 261 patients and 251 healthy individuals. We also investigated the possible association of these SNPs in patients with high-risk jobs and smoking habits with the incidence of bladder cancer. The genotype distributions of IL-6 (-174 C/G) genotype were similar between the cases and the control groups; however, among patients with smoking habits, the association between IL-6 gene polymorphism and incidence of bladder cancer was significant. After a control adjustment for age and sex, the following results were recorded: CC genotype (OR= 2.11, 95%CI=1.56-2.87, p=0.007), GC genotype (OR=2.18, 95%CI=1.16-4.12, p=0.014) and GC+CC (OR=2.6, 95%CI=1.43-4.47, p=0.011). A significant risk of bladder cancer was observed for the heterozygous genotype (AC) of IL-12 (OR=1.47, 95%CI=1.01-2.14, p=0.045) in all cases, and among smokers (AC) (OR=3.13, 95%CI=1.82-5.37, p=0.00014), combined AC+CC (OR=3.05, 95%CI=1.8-5.18, p=0.000015). Moreover among high risk job patients, there was more than a 3-fold increased risk of cancer in the carriers of IL-12 beta heterozygous (OR=3.7, 95%CI=2.04-6.57, p=0.000056) and combined AC+CC(OR=3.29, 95%CI=1.58-5.86, p=0.00002) genotypes as compared with the AA genotype with low-risk jobs. As a conclusion, this study suggests that IL-12(3'UTR A>C) and IL-6 (-174 C>G) genotypes are significantly associated with an increased risk of bladder cancer in the Iranian population with smoking habits and/or performing high-risk jobs.

• YAKHAK HOEJI
• /
• v.54 no.4
• /
• pp.232-239
• /
• 2010

Stems and roots of Acanthopanax koreanum Nakai were extracted with water and treated on immune cells in order to determine their immunomodulatory activites. Various Th-1 type cytokines were measured using ELISA including interleukin (IL)-2, IL-12, interferon-gamma (IFN-$gamma$), and tumor necrosis factor-alpha (TNF-$\alpha$) secreted by dendritic cells, T-cells, intestinal epithelial cells, natural killer cells, and macrophages. As a result, there was a significant increase in IL-12 and IFN-$\gamma$, secretion, but there was no change in the secretion of TNF-$alpha$. Additionally T-cells slightly increased the secretion of IL-2, but there was a significant increase of IL-2 in intestinal epithelial cells. Therefore, our results suggest that A. koreanum Nakai may act as an immunomodulator by stimulating the cell-mediated immunity which can help the immune system defend against infections or cancer cells.