• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.11
• /
• pp.5353-5361
• /
• 2012

Interleukin-18 (IL-18) is an immune-stimulatory cytokine with antitumor activity in preclinical models. It plays pivotal roles in linking inflammatory immune responses and tumor progression and is a useful candidate in gene therapy of lymphoma or lymphoid leukemia. A phase I study of recombinant human IL-18 (rhIL-18) in patients with advanced cancer concluded that rhIL-18 can be safely given in biologically active doses to patients with advanced cancer. Some viruses can induce the secretion of IL-18 for immune evasion. The individual cytokine activity might be potentiated or inhibited by combinations of cytokines. Here we focus on combinational effects of cytokines with IL-18 in cancer progression. IL-18 is an important non-invasive marker suspected of contributing to metastasis. Serum IL-18 may a useful biological marker as independent prognostic factor of survival. In this review we cover roles of IL-18 in immune evasion, metastasis and angiogenesis, applications for chemotherapy and prognostic or diagnostic significance.

• Clinical and Experimental Pediatrics
• /
• v.56 no.7
• /
• pp.271-274
• /
• 2013

Brain insults, including neurotrauma, infection, and perinatal injuries such as hypoxic ischemic encephalopathy, generate inflammation in the brain. These inflammatory cascades induce a wide spectrum of cytokines, which can cause neuron degeneration, have neurotoxic effects on brain tissue, and lead to the development of seizures, even if they are subclinical and occur at birth. Cytokines are secreted by the glial cells of the central nervous system and they function as immune system mediators. Cytokines can be proinflammatory or anti-inflammatory. Interleukin (IL)-$1{\beta}$ and IL-8 are proinflammatory cytokines that activate additional cytokine cascades and increase seizure susceptibility and organ damage, whereas IL-1 receptor antagonist and IL-10 act as anti-inflammatory cytokines that have protective and anticonvulsant effects. Therefore, the immune system and its associated inflammatory reactions appear to play an important role in brain damage. Whether cytokine release is relevant for the processes of epileptogenesis and antiepileptogenesis, and whether epileptogenesis could be prevented by immunomodulatory treatment should be addressed in future clinical studies. Furthermore, early detection of brain damage and early intervention are essential for the prevention of disease progression and further neurological complications. Therefore, cytokines might be useful as biomarkers for earlier detection of brain damage in high-risk infants.

• Journal of Gastric Cancer
• /
• v.2 no.2
• /
• pp.63-68
• /
• 2002

위의 parietal cell 혹은 대식세포와 유사한 세포 내부에서 H. pylori가 발견된다는 보고가 있기는 하나 일반적으로 H. pylori는 Shigella와 같은 침습성 세균은 아닌 것으로 알려져 있다. 그럼에도 불구하고 H. pylori에 감염된 위점막에는 많은 수의 호중구를 위시한 염증세포의 침윤이 관찰되는데 H. pylori가 위상피세포에 부착할 경우 위상피세포를 자극하여 interleukin-8을 위시한 cytokine을 발현케하고 이에 의하여 호중구 등의 염증세포가 몰려들게 된다. 한편 고유층에 몰려든 호중구에서는 다시 interleukin-8을 위시한 일련의 호중구 활성화 chemokine을 분비하여 염증반응을 증폭해 나갈 것이다. 호중구에서 발현되는 myeloperxidase나 활성산소 등도 위점막의 조직 손상에 기여할 것이다. 위상피세포를 덮고 있는 점액층은 위상피세포를 보호한다고 알려져 있으나 H. pylori 감염의 경우 점액층에 의하여 H. pylori의 운동성이 증가하고 이것이 위상피세포로부터의 cytokine 발현을 자극하여 염증반응을 증폭하는 데 관여할 가능성도 있다. H. pylori는 위상피세포에 대하여 apoptosis를 유도함과 동시에 고유층에 몰려든 호중구에 대하여는 apoptosis를 억제케하여 궁극적으로 염증반응을 증폭 및 지속시켜 나가는 쪽으로 작용한다. 한편 H. pylori는 위상피세로로부터 COX-2의 발현을 증가시키는데 이는 위상피세포의 APOPTOSIS를 억제하는 방향으로 작용한다. 이외에 H. pylori의 urease에 의하여 발생한 암모니아나 H. pylori 자신이 분비하는 세포독소가 세포 손상을 유발할 가능성도 있다. 상술한 여러 독성 인자들 중 어느 하나가 단독으로 작용하기보다는 여러 인자가 같이 동시에 또는 시차를 두고 작용할 가능성이 많다고 생각된다.

• Molecular & Cellular Toxicology
• /
• v.1 no.2
• /
• pp.124-129
• /
• 2005

Pro-inflammatory cytokines, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin-12 (IL-12) and interleukin $(IL-1)-{\beta}$, play a key role in causing inflammatory diseases, which are rheumatoid arthritis, Crohn's disease and sepsis. Accumulating evidences suggest that low level laser irradiation (LLLI) may have an anti-inflammatory action. However, there are few data regarding down regulation of Th1 immune response by using the diod typed laser emitting device for human patients. As a fundamental step in order to address this issue, we investigated immunological impact of the low level laser irradiation (10 mw laser diode with a wavelength of 630 nm) on expression of pro-inflammatory cytokines in murine immunocytes (splenocytes and peritoneal macrophages) in vitro. The LLLI on lipopolysaccharide (LPS 100 ng/ml)-stimulated murine splenocytes and macrophages, clearly down regulated mRNA expression of $TNF-{\alpha}$ and IL-12 in dose-dependent manner. In addition, LLLI significantly inhibits the NO production in the LPS-stimulated murine macrophages. This data suggests that LLLI (wavelength of 630 nm) may exert an anti-inflammatory action via modulation of pro-inflammatory cytokine and NO production pathway.

• Journal of Pharmacopuncture
• /
• v.15 no.1
• /
• pp.7-11
• /
• 2012

Aim: Historically, mineral compound herbal medicines have long been used in treatments of immune-related diseases in Korea, China and other Asian countries. In this study, we investigated the anti-inflammatory effect of egg white combined with chalcanthite (IS4) on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Methods: RAW 264.7 cells cultured with LPS and various concentrations of IS4 were analyzed to determine the production of pro-inflammatory cytokines and mediators by using enzyme-linked immune sorbent assays (ELISAs). Results: IS4 concentration inhibited the production of interleukin-1beta (IL-$1{\beta}$), interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF) induced by LPS. IS4 at high concentrations (25 and 50 ${\mu}g/ml$) inhibited, in concentration-dependent manner, the expression of tumor necrosis factor-alpha (TNF-${\alpha}$) stimulated by LPS. Conclusion: IS4 has shown an anti-inflammatory effect in RAW 264.7 cells.

• Journal of Pharmaceutical Investigation
• /
• v.31 no.3
• /
• pp.185-190
• /
• 2001

Human papillomavirus (HPV) infection is known to cause cervical cancers. Human papillomavirus-like particles (VLP) have been studied as preventive vaccines of cervical cancers. To develop VLP as a therapeutic gene carrier, we studied the method to encapsulate cytokine genes in virus-like particles. HPV type 16 capsid L1 genes were amplified by polymerase chain reaction and cloned into T vector. L1 gene was then inserted into baculovirus transfer vector. The clone of baculovirus encoding L1 gene was isolated and used to express L1 protein in Sf 21 insect cells. VLP were purified by CsCl density gradient and ultracentrifugation. VLP were disassembled to capsomer units by treatment of a reducing agent. Given that interleukin-2 (IL-2) genes have been used in anticancer gene therapy and as a molecular adjuvant, IL-2 cytokine plasmids were chosen as a model gene. IL-2 plasmids were incubated with the disassembled capsomer suspension. To reassemble the particles, the mixture of capsomers and cytokine plasmids was dialyzed. The disassembly and reassembly of VLP were confirmed by transmission electron microscopy. The entrapment of cytokine plasmids in reassembled VLP was tested by the stability of plasmids against DNase I. After treatment of reassembled virus-like particles with DNase I, discrete IL-2 DNA band was observed. Our results indicate that IL-2 cytokine plasmid (3.5 kb size) can be encapsulated in the virus-like particles, suggesting the potential of VLP as a gene delivery system. Moreover, VLP containing the adjuvant cytokine plasmids might function as more effective subunit vaccines.

• Analytical Science and Technology
• /
• v.28 no.4
• /
• pp.260-269
• /
• 2015

The protective effects of extract powder of Angelica gigas on the degeneration of the articular cartilage in rats was investigated with monosodium iodoacetate (MIA)-induced osteoarthritis, The treatment of high concentration (50 μg/mL) of Angelica gigas effectively inhibited nitric oxide (NO) production induced by interleukin-1α (IL-1α) without any cytotoxicity. Specifically, mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were dose dependently reduced by extract powder of Angelica gigas. Importantly, mRNA expression in articular cartilage of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were clearly reduced. The inflammatory cytokines in blood were also reduced as well. These results suggested that the protective effects on the degeneration of the articular cartilage was derived from the inhibitory effects of mRNA and protein expression of tested inflammatory cytokines which is linked to prevent the degradation of proteoglycan (PG), the main matrix content in articular cartilage. Meanwhile, the 2 hrs incubation of decursin, a major compound of extract powder in rat whole blood rapidely converted decursin into decursinol which shows string anti-inflammatory activity. The coverted decursinol was detected after 8 hrs in whole blood by LC-MS/MS. Conclusively, the inhibitory effects of inflammatory cytokines production in osteoarthritis may be derived from the production of decursinol, which performs against inflammatroy cytokines like TNF-α, IL-1β, and IL-6.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.26 no.2
• /
• pp.45-57
• /
• 2013

Objectives : Daucus carota sativa has been frequently used as food supplements in many of the Asian countries, and a nutritional medical drug in traditional medicine. This research investigated the effects of Daucus carota sativa extract (DCE) on acute phases of inflammation in Raw 264.7 cells treated with lipopolysaccharide (LPS) in terms of the inhibition of nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) and pro-inflammatory cytokines production. Methods : NO, $PGE_2$, tumor necrosis factor (TNF)-${\alpha}$, interleukin-$1{\beta}$ and interleukin-6 contents were assayed by ELISA, and expressions of inflammation-related proteins such as inducible NO synthase (iNOS) were determined by immunoblot analyses. Results : DCE treatment attenuated the LPS ability to increase the productions of NO and $PGE_2$ as well as the protein level of iNOS in a concentration-dependent manner. Consistently, treatment of the cells with DCE suppressed the production of TNF-${\alpha}$, interleukin-$1{\beta}$ and interleukin-6. DCE also caused decreases of inhibitor of ${\kappa}B{\alpha}$ phosphorylation induced by LPS in the cells, which means DCE inhibition of NF-${\kappa}B$ activity. Furthermore, DCE blocked LPS-induced phosphorylation of p38 and SAPK/JNK. Conclusion : This study showing here may be of help to understand the action mechanism of DCE, and provide the information for the medical use of Daucus carota sativa for the inflammatory disease.

• The Journal of Internal Korean Medicine
• /
• v.39 no.6
• /
• pp.1244-1255
• /
• 2018

Objectives: The purpose of this study is to determine the stimulatory effects of herbal medicines extracts on cytokines release of immune response in immune cells, RAW 264.7 and TK-1 cell. Methods: In a total of 18 extracts, 9 water extracts and 9 ethanol extracts, of herbal medicines, the quantities of polyphenolic compounds were measured and anti-oxidation activities were determined by colorimetric assay. The herbal medicine extracts were treated on RAW 264.7 and TK-1, respectively, and then the releasing changes of tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin-6, and interleukin-10 from both immune cells were determined by the enzyme-linked immunosorbent assay. Results: The polyphenol contents were measured to be 1.56~0.64 mg/g of solids in the two types of extracts with 9 kinds of herbal medicines, while antioxidant activities were found to be 95.62~31.46% as compared with ascorbic acid control. In RAW 264.7 cells treated with herbal medicines extracts, the secretion of $TNF-{\alpha}$ increased to 1.31~1.18 fold, and the amounts of IL-6 were 68.4~97.9% compared with the control group treated with LPS alone. In particular, the secretion amount of anti-inflammatory cytokine IL-10 was suppressed by treatment using herbal medicine extracts. In the case of TK-1 cells, $TNF-{\alpha}$ secretion was suppressed according to the concentrations of herbal extract. The released amounts of IL-10 were shown at 10~40 pg/ml, and increased in a dose-dependent manner. Conclusions: Herbal medicines extracts act on macrophages inducing the secretion of inflammatory cytokine, thereby enhancing the activity of innate immunity. When acting on T cells involved in adaptive immunity, the secretion of anti-inflammatory cytokine is increased to induce the inhibition of the innate immune response.

• Korean Journal of Pharmacognosy
• /
• v.33 no.2 s.129
• /
• pp.124-129
• /
• 2002

The effects of Helicobacter pylori and medicinal plants extract (Leweifang) on the viability and interleukin(IL)-8 production of gastric epithelial cell were investigated. Cells viability was significantly decreased when they incubated with H. pylori or H. pylori toxin. Co-incubation with Leweifang increased H. pylori or H. pylori toxin-inhibited cell growth in a concentration-dependent manner. The production of IL-8 was greatly increased in H. pylori-infected KATO III gastric epithelial cells in a concentration- and time-dependent manner. The increased production of IL-8 was significantly inhibited by Leweifang $(1,000{\sim}5,000{\mu}g/ml)$. These results indicate that Leweifang has protective effect on H. pylori-inhibited cell growth and H. pylori-induced gastric mucosal cell inflammation by suppressing the production of inflammatory cytokine (IL-8) from gastric epithelial cells.