• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.8
• /
• pp.3173-3181
• /
• 2015

Background: It has been hypothesized that IL-18 (pro-) and IL-10 (anti-) inflammatory genetic variants at -607 C/A-137G/C and -819C/T,-592C/A, respectively, may generate susceptibility and severity risk with various modes of tobacco exposure in prostate carcinoma (PCa) patients. IL-18 is a pro-inflammatory cytokine expressed on various cells including prostate gland elements, and is a key mediator of immune responses with anti-cancerous properties. IL-10 is an anti-inflammatory cytokine that is associated with tumour malignancy which causes immune escape. Materials and Methods: The present study was conducted with 540 subjects, comprising 269 prostate carcinoma patients and 271 controls. Genotyping was performed by PCR-RFLP and confirmed by real time PCR probe-based methods. Results: The findings indicated that the mutant heterozygous and homozygous genotype CC and GC+CC showed significant negative associations (p=0.01, OR=0.21; 95% CI: 0.08-0.51 and p=0.011, OR=0.43; 95% CI: 0.22-0.81, respectively) thus, less chance to be diagnosed as cancer against GG genotype of tobacco smoking patients. In addition, a heterozygous GC genotype at the same locus of IL-18 pro-inflammatory cytokine may aggravate the severity (OR=2.82; 95%CI 1.09-7.29 :p=001) so that patients are more likely to be diagnosed in advanced stage than with the GG wild homozygous genotype. Our results also illustrated that anti-inflammatory cytokine (IL-10) genetic variants, although showing no significant association with susceptibility to cancer of the prostate, may gave profound effects on severity of the disease, as -819 TC (OR=4.60; 95%CI 1.35-15.73), and -592 AC (OR=5.04; 95%CI 1.08-25.43) of IL-10 in tobacco chewers and combined users (both chewers and smokers) respectively, are associated with diagnosis in more advanced stage than with other variants. Conclusions: We conclude that promoter genetic variants of IL-18 and IL-10 with various modes of tobacco exposure may affect not only susceptibility risk but also severity in prostate cancer.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.45 no.8
• /
• pp.1099-1106
• /
• 2016

The objective of this study was to evaluate the immunomodulatory activity of crude polysaccharide separated from Cudrania tricuspidata leaf. C. tricuspidata polysaccharide (CTP) was extracted by ethanol precipitation. Immunomodulation activity was tested in macrophage cells (RAW 264.7 and bone-marrow derived macrophage) and splenocytes. CTP treatment significantly increased cell proliferation up to $250{\mu}g/mL$ in both RAW 264.7 and bone-marrow derived macrophages. In this concentration range (below $250{\mu}g/mL$), nitric oxide and cytokine [tumor necrosis factor $(TNF)-{\alpha}$ and interleukin (IL)-6] production also significantly increased. Similarly, splenocyte proliferation dosedependently increased except for the $1,000{\mu}g/mL$ treated group. Regarding cytokine production activity in splenocytes, CTP treatment significantly increased production of Th 1 type cytokines [interferon $(IFN)-{\gamma}$] production but not Th 2 type cytokines (IL-4). Therefore, the results indicate that CTP may have a potential effect on immunomodulatory activity in various immune cells, and this is useful for development of immune enhancing adjuvant materials as a natural ingredient.

• BMB Reports
• /
• v.49 no.6
• /
• pp.305-310
• /
• 2016

Toll-like receptors (TLRs) play a critical role in the innate immune response against pathogens. Each TLR recognizes specific pathogen-associated molecular patterns, after which they activate the adaptor protein MyD88 or TRIF-assembled signaling complex to produce immune mediators, including inflammatory cytokines and type I IFNs. Although the activation of TLR is important for host defense, its uncontrolled activation can damage the host. During the past decade, numerous studies have demonstrated that GSK3β is a key regulator of inflammatory cytokine production in MyD88-mediated TLR signaling via TLR2 and TLR4. Recently, GSK3β has also been implicated in the TRIF-dependent signaling pathway via TLR3. In this review, we describe current advances on the regulatory role of GSK3β in immune responses associated with various TLRs. A better understanding of the role of GSK3β in TLR signaling might lead to more effective anti-inflammatory interventions.

• IMMUNE NETWORK
• /
• v.8 no.1
• /
• pp.1-6
• /
• 2008

Apoptosis signal-regulating kinase 1 (ASK1), a mitogen- activated protein kinase kinase kinase, plays pivotal roles in stress responses. In addition, ASK1 has emerged as a key regulator of immune responses elicited by pathogen-associated molecular patterns (PAMPs) and endogenous danger signals. Recent studies have demonstrated that reactive oxygen species (ROS)-dependent activation of ASK1 is required for LPS-stimulated cytokine production as well as extracellular ATP-induced apoptosis in immune cells. The mechanism of ROS-dependent regulation of ASK1 activity by thioredoxin and TRAFs has been well characterized. In this review, we focus on the molecular details of the activation of ASK1 and its involvement in innate immunity.

• IMMUNE NETWORK
• /
• v.14 no.1
• /
• pp.30-37
• /
• 2014

Collaboration of TLR and non-TLR pathways in innate immune cells, which acts in concert for the induction of inflammatory cytokines, can mount a specific adaptive immune response tailored to a pathogen. Here, we show that murine DC produced increased IL-23 and IL-6 when they were treated with LPS together with curdlan that activates TLR4 and dectin-1, respectively. We also found that the induction of the inflammatory cytokine production by LPS and curdlan requires activation of IKK. However, the same treatment did not induce DC to produce a sufficient amount of TGF-${\beta}$. As a result, the conditioned media from DC treated with LPS and curdlan was not able to direct $CD4^+$ T cells to Th17 cells. Addition of TGF-${\beta}$ but not IL-6 or IL-$1{\beta}$ was able to promote IL-17 production from $CD4^+$ T cells. Our results showed that although signaling mediated by LPS together with curdlan is a potent stimulator of DC to secrete many pro-inflammatory cytokines, TGF-${\beta}$ production is a limiting factor for promoting Th17 immunity.

• Nutrition Research and Practice
• /
• v.14 no.5
• /
• pp.453-462
• /
• 2020

BACKGROUND/OBJECTIVES: Platycodon grandiflorum (PG), an oriental herbal medicine, has been known to improve liver function, and has both anti-inflammatory and antimicrobial properties. However, little is known about the immune-enhancing effects of PG and its mechanism. In this study, we aimed to investigate whether fermented PG extract (FPGE), which has increased platycodin D content, activates the immune response in a murine macrophage cell line, RAW 264.7. MATERIALS/METHODS: Cell viability was determined by Cell Counting Kit-8 assay and the nitric oxide (NO) levels were measured using Griess reagent. Cytokine messenger RNA levels of were monitored by quantitative reverse transcription polymerase chain reaction. To investigate the molecular mechanisms underlying immunomodulatory actions of FPGE in RAW 264.7 cells, we have conducted luciferase reporter gene assay and western blotting. RESULTS: We found that FPGE treatment induced macrophage cell proliferation in a dose-dependent manner. FPGE also modulated the expression of NO and pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The activation and phosphorylation levels of nuclear factor kappa B (NF-κB) were increased by FPGE treatment. Moreover, 5-aminoimidazole-4-carboxamide ribonucleotide, an activator of AMP-activated kinase (AMPK), significantly reduced both lipopolysaccharides- and FPGE-induced NF-κB reporter gene activity. CONCLUSIONS: Taken together, our findings suggest that FPGE may be a novel immune-enhancing agent acting via AMPK-NF-κB signaling pathway.

• Korean Journal of Pharmacognosy
• /
• v.31 no.2
• /
• pp.142-148
• /
• 2000

The purpose of this research was to investigate effects of Samultang water extract (SMT) on cytokine production from immune cells during the late stage of pregnancy in BALB/c mice. SMT(500 mg/kg) was administered p.o. once a day for 7 days, and then thymocytes and peritoneal macrophages were separated. At the late stage of pregnant mice, the proliferation of thymocytes and the production of ${\gamma}-interferon$ in thymocytes were decreased as compared with normal group, but the production of interleukin-2 and interleukin-4 was increased. The production of tumor necrosis $factor-{\alpha}$, nitric oxide and phagocytic activity in peritoneal macrophage was increased as compared with normal group. At the late stage of pregnant mice administered with SMT, the production of interleukin-2 in thymocytes was decreased as compared with a pregnant group, but the proliferation of thymocytes, the production of ${\gamma}-interferon$ and interleukin-4 was increased. The production of tumor necrosis $factor-{\alpha}$ and nitric oxide in peritoneal macrophages were decreased as compared with a pregnant group, but phagocytic activity were increased. These results suggest that SMT has the regulative action on immune function of thymocytes and peritoneal macrophages at the late stage of pregnant mice.

• IMMUNE NETWORK
• /
• v.6 no.1
• /
• pp.6-12
• /
• 2006

Background: The Hypothalamo-Pituitary-Adrenal (HPA) axis is an important regulator for the body's stress response. As a primary stress responsive system, HPA-axis secretes various neurotransmitters, hormones, and cytokines, which regulates the immune system. Natural killer (NK) cell which is plays an important role in the innate immune response, is specially decreased their numbers and loose cytolytic activity in response to stress. However, the effect of HPA-axis secreted proteins on NK cell activity has not been defined. Herein, we studied the effect of adrenal secreted adiponectin on NK cell cytotoxicity. Adiponectin which is well-known metabolic control protein, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. Methods: Signal sequence trap was used to find stress novel secretory protein from HP A-axis. Selected adiponectin was treated mouse mature primary NK cells and then examined the effect of adiponectin to NK cell cytotoxicity and cytokine expression level. Results: We found that adiponectin which is secreted from adrenal gland, suppress IL-2 induced NK cell cytotoxicity. And also investigated cytolytic cytokines are suppressed by adiponectin. Conclusion: These data suggest that adiponectin inhibites NK cell cytotoxicity via suppression of cytotoxicity related target gene.

• Journal of Acupuncture Research
• /
• v.34 no.2
• /
• pp.39-48
• /
• 2017

Objectives : In this study, we investigated the immunomodulatory and antioxidant effect of MOK, a pharmacopuncture medicine, in concanavalin A (Con A)-stimulated mouse splenocytes. Methods : Primary splenocytes were isolated from ICR mice. The splenocytes were treated with MOK extract (1.25, 2.5, 5, 10, and 20 mg/mL) for 30 min and then stimulated with Con A (200 ng/mL) for the indicated times. Cell viability of the splenocytes was measured using an MTT assay. The mRNA expression of Th1/Th2 cytokines ($IFN-{\gamma}$, IL-4, IL-10, and Foxp3) and antioxidant enzymes (HO-1 and MnSOD) was measured by RT-PCR. Results : Addition of MOK extract at 2.5, 5, and 10 mg/mL in Con A-stimulated splenocytes significantly decreased the production of $IFN-{\gamma}$ and significantly increased the expression of IL-4, IL-10, and Foxp3 mRNA. MOK extract also increased the mRNA expression of HO-1 and MnSOD in splenocytes. Conclusion : MOK extract modulated the Th1/Th2 immune response via the regulation of cytokine levels in splenocytes and exerted an antioxidant effect via the upregulation of antioxidant proteins.

• Food Science and Biotechnology
• /
• v.18 no.1
• /
• pp.218-222
• /
• 2009

Ability of water extract from Prunella vulgaris Labiatae to stimulate immune system and inhibit tumor metastasis in mice was assessed. In experimental lung metastasis, prophylactic intravenous (i.v.) administration of water extract from P. vulgaris significantly inhibited lung metastasis in a dose-dependant manner. Peritoneal macrophages stimulated with P. vulgaris produced various cytokines such as tumor necrosis factor (TNF)-$\alpha$ and interlukin (IL)-12 as well as induced tumoricidal activity. In an assay for natural killer (NK) cell activity, i.v. administration of P. vulgaris significantly augmented NK cytotoxicity. The depletion of NK cells by injection of rabbit anti-asialo GM1 serum abolished the inhibitory effect of P. vulgaris on lung metastasis of colon26-M3.1 cells. These data demonstrate that P. vulgaris activate innate immune system to inhibit the growth of foreign materials including tumor cells in mice.