• IMMUNE NETWORK
• /
• 제12권6호
• /
• pp.230-239
• /
• 2012

Activation-induced cytidine deaminase (AID) is an enzyme that is predominantly expressed in germinal center B cells and plays a pivotal role in immunoglobulin class switch recombination and somatic hypermutation for antibody (Ab) maturation. These two genetic processes endow Abs with protective functions against a multitude of antigens (pathogens) during humoral immune responses. In B cells, AID expression is regulated at the level of either transcriptional activation on AID gene loci or post-transcriptional suppression of AID mRNA. Furthermore, AID stabilization and targeting are determined by post-translational modifications and interactions with other cellular/nuclear factors. On the other hand, aberrant expression of AID causes B cell leukemias and lymphomas, including Burkitt's lymphoma caused by c-myc/IgH translocation. AID is also ectopically expressed in T cells and non-immune cells, and triggers point mutations in relevant DNA loci, resulting in tumorigenesis. Here, I review the recent literatures on the function of AID, regulation of AID expression, stability and targeting in B cells, and AID-related tumor formation.

• 대한의생명과학회지
• /
• 제21권4호
• /
• pp.218-226
• /
• 2015

The present study investigated the mechanisms of licochalcone B (LicB)-mediated inhibition of the inflammatory response in murine macrophages. RAW264.7 murine macrophages were cultured in the absence or presence of lipopolysacharide (LPS) with LicB. LicB suppressed the generation of nitric oxide and the pro-inflammatory cytokines interleukin (IL)-$1{\beta}$, IL-6 and tumor necrosis factor-${\alpha}$. LicB also inhibited the expression of mRNA for inducible nitric oxide synthase and pro-inflammatory cytokines induced by LPS. Moreover, LicB inhibited nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and activator protein-1 translocation into the nucleus in a dose-dependent manner. Thus, LicB mainly exerts its anti-inflammatory effects by inhibiting the LPS-induced NF-${\kappa}B$ and activator protein-1 signaling pathways in macrophages, which subsequently diminishes the expression and release of various inflammatory mediators. LicB shows promise as a therapeutic agent in inflammatory diseases.

• Biomolecules & Therapeutics
• /
• 제20권2호
• /
• pp.144-151
• /
• 2012

The molecular mechanisms by which a variety of naturally-occurring dietary compounds exert chemopreventive effects have been a subject of intense scientific investigations. Induction of phase II detoxification and anti-oxidant enzymes through activation of Nrf2/ARE-dependent gene is recognized as one of the major cellular defense mechanisms against oxidative or xenobiotic stresses and currently represents a critical chemopreventive mechanism of action. In the present review, the functional significance of Keap1/Nrf2 protein module in regulating ARE-dependent phase II detoxification and anti-oxidant gene expression is discussed. The biochemical mechanisms underlying the phosphorylation and expression of Keap1/Nrf2 proteins that are controlled by the intracellular signaling kinases and ubiquitin-mediated E3 ligase system as well as control of nucleocytoplasmic translocation of Nrf2 by its innate nuclear export signal (NES) are described.

• Fisheries and Aquatic Sciences
• /
• 제17권1호
• /
• pp.27-35
• /
• 2014

Marine brown algae have been identified as a rich source of structurally diverse bioactive compounds. Whether Myagropsis yendoi ethanolic extracts (MYE) inhibit inflammatory responses was investigated using lipopolysaccharide (LPS)-stimulated microglia BV-2 cells. MYE inhibited LPS-induced nitric oxide (NO) production in a dose-dependent manner and suppressed the expression of inducible nitric oxide synthase in BV-2 cells. MYE also reduced the production of pro-inflammatory cytokines in LPS-stimulated BV-2 cells. LPS-induced nuclear factor-${\kappa}B$ (NF-${\kappa}B$) transcriptional activity and NF-${\kappa}B$ translocation into the nucleus were significantly inhibited by MYE treatment through preventing degradation of the inhibitor ${\kappa}B-{\alpha}$. Moreover, MYE inhibited the phosphorylation of AKT, ERK, JNK, and p38 mitogen-activated protein kinase in LPS-stimulated BV-2 cells. These results indicate that MYE is a potential source of therapeutic or functional agents for neuroinflammatory diseases.

• Journal of Plant Biology
• /
• 제33권1호
• /
• pp.81-84
• /
• 1990

The chloroplast has been the prime light-energy harvesting organelle on earth. It also carries out several key metabolic processes, such as lipid synthesis and nitrogen metabolism. Even though the chloroplast has its own genome, its coding capacity can afford only dozens of proteins, and most of the proteins functioning in the chloroplast are imported from the cytosol where nuclear encoded chloroplast genes are synthesized on free cytosokic ribosomes. Precursor proteins synthesized on cytosolic ribosomes have transit peptides at the amino termini of the proteins, and the transit peptide is sufficient to transfer chloroplast proteins from the cytosol into the chloroplast. When comparing amino acid sequences duduced from the nucleotide sequences of the clones of the chloroplast proteins, high homologies can be found among the transit peptides of proteins with the same function. Overall amino acid compositions of the transit peptides show amphiphilic characters of the transit peptides, and the amphiphilicity indicates that three dimensional structure of the transit peptide is responsible for the translocation of the chloroplast proteins.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.99.1-99.1
• /
• 2003

Cinnamaldehyde is the main component of cinnamon bark oil and show several biological activities such as anti-tumor, anti-fungal, anti-mutagenic and anti-inflammatory effects. A couple of studies have investigated how the natural compound exerts its anti-inflammatory effect. In despite of numerous investigations, the biological mechanism of effects belong to cinnamaldehyde remain unclear. We isolated 2-hydroxycinnamaldehyde(HCA) from the bark of Cinnamomun cassia Blume and reported a various of biological activities of HCA. (omitted)

• Tuberculosis and Respiratory Diseases
• /
• 제42권6호
• /
• pp.801-812
• /
• 1995

CR asthma is associated with disease chronicity, a positive family history of asthma and in vitro and in vivo defects in mononuclear cell function. The HPA axis in CR asthmatics is suppressed normally by dexamethasone and the pharmacokinetic profile of an oral dose of prednisolone is similar to that found in CS subjects. In addition, competitive binding studies have shown that the ligand binding and nuclear translocation functions of the GR are similar in the two groups. Studies using gel retardation assay have indicated a defect in DNA binding in CR subjects. Chemical mutational analysis of the GR has shown that is not due to a defect in its structure at the cDNA level. Scatchard analysis of the GR/DNA and GR/ligand interactions suggests that there may be transcriptional interference of the GR with other transcriptionally active molecules leading to defective gene transcription.

• Clinical and Experimental Pediatrics
• /
• 제45권9호
• /
• pp.1106-1113
• /
• 2002

목 적: 전사인자 $NF-{\kappa}B$는 스트레스 등으로부터 세포 자멸사를 조절하여 적응을 유지하는 기본적인 분자로 인식되고 있다. 저산소증 상태는 많은 심장병에서 동반되는 병변으로 성장인자 VEGF와 IGF-I는 저산소증 시에 심장을 보호하는 작용을 할 것으로 추측되고 있다. 본 연구에서는 저산소증과 같은 자극으로부터 심장의 보호 기능이 추정된 $NF-{\kappa}B$의 발현과 함께 VEGF와 IGF-I의 발현 연관성을 검토하여 분자 생물학적인 기전을 이해하고자 하였다. 방 법 : 실험동물로 Sprague Dawley rat을 이용하여, 저산소 자극은 8%의 산소와 92% 질소를 hypoxic chamber로 관류시키며 유도하였다. 심장에 대한 저산소증 자극 후 심근세포로부터 측정 인자들과 관련된 핵 내 단백질, 전단백질 그리고 mRNA를 분리하였다. 핵 내의 전사인자는 EMSA로 측정하였으며, VEGF와 IGF-I의 발현은 competitive-PCR, Western hybridization, Northern hybridization으로 확인하였다. 또한 이러한 성장인자의 발현과 관련된 $NF-{\kappa}B$의 기능을 확인하기 위하여 $NF-{\kappa}B$의 핵 내 이동 억제제인 DDTC를 전 처치로 복강 내 주사하여 그에 따른 VEGF 및 IGF-I의 발현 양상을 비교하였다. 결 과 : 저산소 자극 후에 심근 세포 내에 전사인자 $NF-{\kappa}B$, AP-1, NF-ATc의 활성이 증가되었다. VEGF와 IGF-I의 발현도 저산소증 자극 시 증가되었지만, DDTC 전 처치에 의한 $NF-{\kappa}B$의 핵 내 이동 차단 후 이들 인자의 발현은 의의 있게 감소하였다. 결 론 : 전사인자 $NF-{\kappa}B$는 저산소증 상태에서 그 활성이 증가하고 저산소증 상태와 같은 심장에 대한 이상 자극 시 VEGF와 IGF-I의 발현을 증가시켜 심장을 보호하는 것으로 추정된다.

• Journal of Nutrition and Health
• /
• 제51권4호
• /
• pp.323-329
• /
• 2018

만성 염증은 현대사회에서 다양한 질병을 유발하는 주요 원인으로 작용하기 때문에 항염증 활성을 가진 소재의 연구는 염증 관련 질병의 예방과 치료에 있어서 중요하다. 본 연구에서는 LPS에 의해 염증을 유도한 RAW 264.7 세포에서 제주왕지네 (Scolopendra subspinipes mutilans) 에탄올 추출물의 염증 조절 기전을 확인하여 항염증 소재로서의 가능성을 조사하였다. LPS에 의해 증가된 NO 생성과 iNOS 발현은 왕지네 추출물에 의해 감소되었고 pro-inflammatory cytokine으로 알려진 $IL-1{\beta}$, IL-6의 발현에서도 유사한 결과를 보였다. 왕지네 추출물은 LPS에 의해 유도된 $NF-{\kappa}B$의 핵으로의 전이와 $I{\kappa}B$의 분해를 동시에 억제하였고 $NF-{\kappa}B$ inhibitor의 처리는 NO 생성과 iNOS 발현을 더욱 억제하였다. 이상의 결과는 왕지네 추출물이 $NF-{\kappa}B$ 활성 조절을 통해 염증 반응의 지표로 사용되는 NO 생성 및 pro-inflammatory cytokine의 발현을 효과적으로 억제하여 항염 활성을 가진 소재로서의 가능성을 보여주는 것으로 염증에 의해 유발되는 다양한 질병을 효율적으로 제어하는 소재를 개발하는데 있어서 주요한 정보를 제공할 것으로 생각된다.

• Journal of Microbiology and Biotechnology
• /
• 제30권1호
• /
• pp.85-92
• /
• 2020

One of the omega-3 essential fatty acids, docosahexaenoic acid (DHA), is a significant constituent of the cell membrane and the precursor of several potent lipid mediators. These mediators are considered to be important in preventing or treating several diseases. Resolvin D5, an oxidized lipid mediator derived from DHA, has been known to exert anti-inflammatory effects. However, the detailed mechanism underlying these effects has not yet been elucidated in human monocytic THP-1 cells. In the present study, we investigated the effects of resolvin D5 on inflammation-related signaling pathways, including the extracellular signal-regulated kinase (ERK)-nuclear factor (NF)-κB signaling pathway. Resolvin D5 downregulated the production of interleukin (IL)-6 and chemokine (C-C motif) ligand 5 (CCL5). Additionally, these inhibitory effects were found to be modulated by mitogen-activated protein kinase (MAPK) and NF-κB in lipopolysaccharide (LPS)-treated THP-1 cells. Resolvin D5 inhibited the LPS-stimulated phosphorylation of ERK and translocation of p65 and p50 into the nucleus, resulting in the inhibition of IL-6 and CCL5 production. These results revealed that resolvin D5 exerts anti-inflammatory effects in LPS-treated THP-1 cells by regulating the phosphorylation of ERK and nuclear translocation of NF-κB.