• Title/Summary/Keyword: interleukin-10(IL-10)

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Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

  • Kuppala, Manohar Babu;Syed, Sunayana Begum;Bandaru, Srinivas;Varre, Sreedevi;Akka, Jyothy;Mundulru, Hema Prasad
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5353-5361
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    • 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.

High-Level Expression of Recombinant Human Interleukin-2 in Chinese Hamster Ovary Cells Using the Expression System Containing Transcription Terminator

  • Kim, Eun-Ju;Kim, Dong-Jun;Hwang, Hye-Yeon;Yoon, Jae-Seung;Yoon, Ye-Up;Baek, Kwang-Hee
    • Journal of Microbiology and Biotechnology
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    • v.14 no.4
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    • pp.810-815
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    • 2004
  • Many biological properties and the clinical potential of human interleukin-2 (hIL-2) draw much attention to its high-level expression in mammalian cells. Recombinant human IL-2 (rhIL-2) was expressed in Chinese hamster ovary (CHO) cells, using the recently developed expression system which confers position-independent expression. Stable CHO cell lines carrying several hundred amplified copies of the rhIL-2 gene were easily obtained and rhIL-2 was expressed at high levels after selection with increasing concentrations of methotrexate. Interestingly, the insertion of the transcription terminator of the human gastrin gene into the downstream region of the gene for rhIL-2 considerably increased rhIL-2 expression. Using the expression system with the transcription terminator, it was possible to get a CHO cell line expressing the rhIL-2 at a very high level, about $11.4\mug/10^6$ cell/day, which is about 6 times higher than that previously reported. The biological activity of the rhIL-2 protein purified from the cell line was also confirmed by the cell proliferation assay.

The Relationship Between Interleukin $1{\beta}$ Gene Polymorphism and Renal Involvement in Henoch-$Sch\ddot{o}nlein$ Purpura (Henoch-$Sch\ddot{o}nlein$ Purpura에서 Interleukin $1{\beta}$ 유전자 다형성과 신장 침범과의 연관성)

  • Na, Hyoung-Joon;Go, Il-Yong;Yoon, Joon-Ho;Yeh, Byung-Il;Kim, Hwang-Min
    • Childhood Kidney Diseases
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    • v.10 no.2
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    • pp.125-131
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    • 2006
  • Purpose : High interleukin-1 beta(IL-$1{\beta}$) expression in the skin biopsy specimens of patients with Henoch-$Sch\ddot{o}nlein$ Purpura(HSP) has been observed. We examined IL-$1{\beta}$ gene polymorphism in patients with HSP. The purpose of this study is to examine the relationship between IL-$1{\beta}$ gene polymorphism and renal involvement in HSP. Methods : Patients from mideast Korea with HSP were studied. All patients had at least 6 months of follow up. Patients and ethnically matched controls were genotyped for IL-$1{\beta}$ gene polymorphism by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Results : Thirty-four patients(all younger than 15 years old) who had been diagnosed with HSP and 27 controls were examined. No allele or genotype differences between the HSP and control groups were observed. No significant association between the carriage of IL-$1{\beta}$(-511) T allele and renal involvement(P=0.525, OR:1.417, CI:0.545-3.686) was found. Conclusion : In unselected patients with HSP, carriage of IL-$1{\beta}$(-511) T allele does not appear to influence renal involvement.

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Role of Interleukin-4 (IL-4) in Respiratory Infection and Allergy Caused by Early-Life Chlamydia Infection

  • Li, Shujun;Wang, Lijuan;Zhang, Yulong;Ma, Long;Zhang, Jing;Zu, Jianbing;Wu, Xuecheng
    • Journal of Microbiology and Biotechnology
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    • v.31 no.8
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    • pp.1109-1114
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    • 2021
  • Chlamydia pneumoniae is a type of pathogenic gram-negative bacteria that causes various respiratory tract infections including asthma. Chlamydia species infect humans and cause respiratory infection by rupturing the lining of the respiratory which includes the throat, lungs and windpipe. Meanwhile, the function of interleukin-4 (IL-4) in Ch. pneumoniae respiratory infection and its association with the development of airway hyperresponsiveness (AHR) in adulthood and causing allergic airway disease (AAD) are not understood properly. We therefore investigated the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. In this study, Ch. pneumonia strain was propagated and cultured in HEp-2 cells according to standard protocol and infant C57BL/6 mice around 3-4 weeks old were infected to study the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. We observed that IL-4 is linked with Chlamydia respiratory infection and its absence lowers respiratory infection. IL-4R α2 is also responsible for controlling the IL-4 signaling pathway and averts the progression of infection and inflammation. Furthermore, the IL-4 signaling pathway also influences infection-induced AHR and aids in increasing AAD severity. STAT6 also promotes respiratory infection caused by Ch. pneumoniae and further enhanced its downstream process. Our study concluded that IL-4 is a potential target for preventing infection-induced AHR and severe asthma.

Anti-inflammatory effects of the Rubus occidentalis seed extracts on UV-B induced inflammation in HaCat cells (각질형성세포에서 UV-B와 사이토카인에 의하여 유도되는 염증 반응에 대한 복분자 씨앗 추출물의 항염증 효과)

  • Kim, Dong-Hee;Park, Tae-Soon;Son, Jun-Ho
    • Journal of Applied Biological Chemistry
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    • v.59 no.3
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    • pp.247-253
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    • 2016
  • It confirmed the applicability as an anti-inflammatory material from Rubus occidentalis seed (RSE) extract. In HaCaT cells to evaluate the anti-inflammatory potential as a material RSE extract on the activity of the inflammatory factors caused by UVB and $IFN-{\gamma}/TNF-{\alpha}$. We measured the activity of ROS, interleukin-$1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6) and interleukin-8 (IL-8) by ROS-Glo $H_2O_2$ assay and ELISA kit. Our results showed that the RSE extracts inhibit the UVB and $IFN-{\gamma}/TNF-{\alpha}$-induced ROS activities and expression of $IL-1{\beta}$, IL-6 and IL-8 in a dose-dependent manner. Also it was found that inflammatory mediators of the expression of cyclooxygenase-2 (COX-2) inhibition were also brought, the expression of which is increased $PGE_2$ by COX-2 also inhibited. Finally RSE extracts measure the seed expression of filaggrin in the skin barrier, the main factor of the extract could be confirmed to increase the expression of the filaggrin damaged as a result of this concentration-dependent manner. Through this, it was able to confirm that the efficacy RSE extract to protect the inflammation by restoring the damaged layers of the epidermis. Results from more than RSE extract was able to confirm that the extract that has anti-inflammatory effects by improving the inflammation being produced from UVB.

Novel Variations in Human Interleukin-29 and Their Association (사람의 Interleukin-29 유전자의 새로운 변이의 단리 및 그들의 연관)

  • Song, Ju-Hee;Chae, Soo-Cheon;Lee, Jae-Hoon;Chung, Hun-Taeg
    • Journal of Life Science
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    • v.14 no.2
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    • pp.275-279
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    • 2004
  • Gene polymorphisms of cytokines and their receptors are attractive candidates as genetic factors in the pathogenesis of immune-mediated diseases and have been reported to be associated with disease susceptibility to autoimmune, inflammatory and infectious diseases. IL-29 is one of important candidate genes for complex trait of genetic diseases but there is no published survey of single nucleotide polymorphisms (SNPs) in this gene. In this study, for the first time, we have examined the full genomic sequence of IL-29 including the promoter regions to identify SNPs. We examined the frequencies of genotypes and alleles at the SNP site of IL-29 in allergic rhinitis patients and non-allergic rhinitis controls using the direct sequencing method to determine whether this IL-29 SNP is associated with allergic rhinitis in Korean population. We identified one novel SNP (1184C>A) in the intron 2 and one novel variation site (-1842_-1841dupGA) in the promoter region of human IL-29 gene. The P values of SNP or variation site were not significant between the healthy controls and allergic rhinitis patients. Our results suggest that the 1184C>A polymorphism and -1842_-1841dupGA variation site in human IL-29 gene were not associated to allergic rhinitis.

Functions of Metallothionein Generating Interleukin-10-Producing Regulatory $CD4^{+}T$ Cells Potentiate Suppression of Collagen-Induced Arthritis

  • Huh, Sung-Jin;Lee, Kyu-Heon;Yun, Hye-Sun;Paik, Doo-Jin;Kim, Jung-Mogg;Youn, Jee-Hee
    • Journal of Microbiology and Biotechnology
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    • v.17 no.2
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    • pp.348-358
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    • 2007
  • Metallothionein, a cysteine-rich stress response protein that is naturally induced by a variety of immunologic stressors, has been shown to suppress autoimmune disorders through mechanisms not yet fully defined. In the present study, we examined the underlying mechanisms by which metallothionein might mediate such regulation of autoimmunity. $Na\ddot{i}ve\;CD4^+$ T cells from metallothionein-deficient mice differentiated to produce significantly less IL-10, $TGF-{\gamma}$, and repressor of GATA, but more $IFN-{\gamma}$ and T-bet, when compared with those from wild-type mice. The levels of IL-4 and GATA-3 production were not different between the two groups of mice. Conversely, treatment with exogenous metallothionein during the priming phase drove $na\ddot{i}ve$ wild-type $CD4^+\;T$ cells to differentiate into cells producing more IL-10 and $TGF-{\beta}$, but less $IFN-{\gamma}$ than untreated cells. Metallothionein-primed cells were hyporesponsive to restimulation, and suppressive to T cell proliferation in an IL-10-dependent manner. Lymphocytes from metallothionein-deficient mice displayed significantly elevated levels of AP-1 and JNK activities in response to stimulation compared with those from wild-type controls. Importantly, transgenic mice overexpressing metallothionein exhibited significantly reduced susceptibility to collagen-induced arthritis and enhanced IL-10 level in the serum, relative to their nontransgenic littermates. Taken together, these data suggest that metallothionein is able to promote the generation of IL-10-and $TGF-{\beta}$-producing type 1 regulatory T-like cells by downregulating JNK-dependent AP-1 activity. Thus, metallothionein may play an important role in the regulation of Th1-dependent autoimmune arthritis, and may represent both a potential target for therapeutic manipulation and a critical element in the diagnostic assessment of disease potential.

Lipoteichoic Acid Isolated from Lactobacillus plantarum Maintains Inflammatory Homeostasis through Regulation of Th1- and Th2- Induced Cytokines

  • Ahn, Ji Eun;Kim, Hangeun;Chung, Dae Kyun
    • Journal of Microbiology and Biotechnology
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    • v.29 no.1
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    • pp.151-159
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    • 2019
  • Lipoteichoic acid isolated from Lactobacillus plantarum K8 (pLTA) alleviates lipopolysaccharide (LPS)-induced excessive inflammation through inhibition of $TNF-{\alpha}$ and interleukin (IL)-6. In addition, pLTA increases the survival rate of mice in a septic shock model. In the current study, we have found that pLTA contributes to homeostasis through regulation of pro- and anti-inflammatory cytokine production. In detail, pLTA decreased the production of IL-10 by phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells stimulated with prostaglandin E2 (PGE-2) and LPS. However, $TNF-{\alpha}$ production which was inhibited by PGE-2+LPS increased by pLTA treatment. The regulatory effects of IL-10 and $TNF-{\alpha}$ induced by PGE-2 and LPS in PMA-differentiated THP-1 cells were mediated by pLTA, but not by other LTAs isolated from either Staphylococcus aureus (aLTA) or L. sakei (sLTA). Further studies revealed that pLTA-mediated IL-10 inhibition and $TNF-{\alpha}$ induction in PGE-2+LPS-stimulated PMA-differentiated THP-1 cells were mediated by dephosphorylation of p38 and phosphorylation of c-Jun N-terminal kinase (JNK), respectively. Reduction of pLTA-mediated IL-10 inhibited the metastasis of breast cancer cells (MDA-MB-231), which was induced by IL-10 or conditioned media prepared from PGE-2+LPS-stimulated PMA-differentiated THP-1 cells. Taken together, our data suggest that pLTA contributes to inflammatory homeostasis through induction of repressed pro-inflammatory cytokines as well as inhibition of excessive anti-inflammatory cytokines.

Induction of IL-8 and reactive oxygen species in periodontal ligament cells by Aggregatibacter actinomycetemcomitans (치주인대세포에서 Aggregatibacter actinomycetemcomitans의 IL-8 및 활성산소종 유도능)

  • Lee, Yang-Sin;Park, Hong-Gyu;Kim, Sung-Whan;Cha, Jeong-Heon;Yoo, Yun-Jung
    • Journal of Periodontal and Implant Science
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    • v.39 no.3
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    • pp.331-337
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    • 2009
  • Purpose: Interleukin (IL)-8 is one of pro-inflammatory cytokines. Reactive oxygen species (ROS) are reduced metabolites of $O_2$. Aggregatibacter actinomycetemcomitans is one of representative periodontopathogens. To investigate the role of A. actinomycetemcomitans in IL-8 expression of periodontal ligament (PDL) cells, we estimated the production of IL-8 and ROS in A. actinomycetemcomitans treated PDL cells. Methods: The IL-8 production was determined by enzyme-linked immunosorbent assay. The ROS production was estimated using H2DCFDA and FACS. Results: A. actinomycetemcomitans increased the production of IL-8 and ROS at 10, 100, and 500 multiplicity of infection. N-acetylcysteine, an antioxidant of ROS, down-regulated the production of IL-8 induced by A. actinomycetemcomitans. Conclusions: These results suggest that A. actinomycetemcomitans induces IL-8 production and ROS may act as a mediator in this process.

The immune-enhancement effect by Falun Gong cultivation

  • Jeong, Hyun-Ja;Kang, Ji-Seok;Kim, Hyung-Min;Lee, Ki-Nam
    • Advances in Traditional Medicine
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    • v.2 no.2
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    • pp.113-118
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    • 2002
  • Falun Gong (FG) is an advanced system of cultivation and practice, which is beneficial for both mind and body. In this study we investigated the effects of FG on the production of cytokines in FG practitioner (FGP). To study whether plasma cytokines levels were affected by FG, their levels were analyzed. The amount of $interferon-{\gamma}$ $(IFN-{\gamma})$, interleukin (IL)-2, IL-4 and IL-6 (2.5-fold for $IFN-{\gamma}$, 1.2-fold for IL-2, 2.1-fold for IL-4 and 2.5-fold for IL-6, respectively) were significantly higher in the FGP group than normal group (P<0.05). Peripheral blood mononuclear cells obtained from normal healthy control and FGP were cultured for 24 h in the presence or absence of lipopolysaccharide. The amount of $IFN-{\gamma}$, IL-2, IL-4 and IL-6 in culture supernatant was quantified. However, there were no significant differences in the level of the same cytokines between the normal and FGP group. These data suggest that FG cultivation may contribute to immune-enhancement in vivo.