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Kim, Hyun-Jin,Lee, Young-Hee,Im, Sun-A,Kim, Kyungjae,Lee, Chong-Kil The Korean Association of Immunobiologists 2010 Immune Network Vol.10 No.3
Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve pain, reduce fever and inhibit inflammation. NSAIDs function mainly through inhibition of cyclooxygenase (COX). Growing evidence suggests that NSAIDs also have immunomodulatory effects on T and B cells. Here we examined the effects of NSAIDs on the antigen presenting function of dendritic cells (DCs). Methods: DCs were cultured in the presence of aspirin or ibuprofen, and then allowed to phagocytose biodegradable microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using OVA-specific CD8 and CD4 T cells. Results: Aspirin and ibuprofen at high concentrations inhibited both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens. Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs. Ibuprofen rather increased the expression level of total MHC molecules and co-stimulatory molecules on DCs. Conclusion: These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.
Specific anti-tumor activities in venom peptides of lesser paper wasp Parapolybia varia
Kyungjae Andrew Yoon,Kyungmun Kim,A-Young Kim,Young Han Park,Woo Young Bang,Chang Mu Kim,Young Ho Koh,Si Hyeock Lee 한국응용곤충학회 2016 한국응용곤충학회 학술대회논문집 Vol.2016 No.04
The lesser paper wasp, Parapolybia varia, belongs to large subfamily Polistinae and is distributed in Middle East, the Indo-Papuan region and East Asia. P. varia is known to become aggressive when disturbed for defending their colonies, resulting in fatal envenomation. Vespid chemotactic peptide (VCP) and vespakinin have recently been determined to be the top two genes most abundantly transcribed in venom glands of P. varia. To investigate the pharmacological and toxicological properties of VCP and vespakinin, their antitumor, antimicrobial, and cytotoxic activities were evaluated. VCP exhibited a significantly high antitumor activity against ovarian tumor cell SK-OV-3 at 100 M. VCP also showed higher hemolytic activity than vespakinin. Antimicrobial activity was only observed with VCP against yeast Candida albicans at 1 mM. Since VCP showed a relatively low hemolytic activity but a considerable level of antitumor activity, it has further merits to be exploited as a potential antitumor agent with reduced side effects on normal cells.
Kim, Seulah,Shin, Seulmee,Hyun, Bobae,Kong, Hyunseok,Han, Shinha,Lee, Aeri,Lee, Seungjeong,Kim, Kyungjae The Korean Association of Immunobiologists 2012 Immune Network Vol.12 No.5
Dioscoreae Rhizome (DR) has been used in traditional medicine to treat numerous diseases and is reported to have anti-diabetes and anti-tumor activities. To identify a bioactive traditional medicine with anti-inflammatory activity of a water extract of DR (EDR), we determined the mRNA and protein levels of proinflammatory cytokines in macrophages through RT-PCR and western blot analysis and performed a FACS analysis for measuring surface molecules. EDR dose-dependently decreased the production of NO and pro-inflammatory cytokines such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, and $PGE_2$, as well as mRNA levels of iNOS, COX-2, and pro-inflammatory cytokines, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as B7-1 and B7-2 was also reduced by EDR. Furthermore, activation of the nuclear transcription factor, NF-${\kappa}B$, but not that of IL-4 and IL-10, in macrophages was inhibited by EDR. These results show that EDR decreased pro-inflammatory cytokines via inhibition of NF-${\kappa}B$-dependent inflammatory protein level, suggesting that EDR could be a useful immunomodulatory agent for treating immunological diseases.
PLCγ1 in dopamine neurons critically regulates striatal dopamine release via VMAT2 and synapsin III
Kim Hye Yun,Lee Jieun,Kim Hyun-Jin,Lee Byeong Eun,Jeong Jaewook,Cho Eun Jeong,Jang Hyun-Jun,Shin Kyeong Jin,Kim Min Ji,Chae Young Chan,Lee Seung Eun,Myung Kyungjae,Baik Ja-Hyun,Suh Pann-Ghill,Kim Jae- 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Dopamine neurons are essential for voluntary movement, reward learning, and motivation, and their dysfunction is closely linked to various psychological and neurodegenerative diseases. Hence, understanding the detailed signaling mechanisms that functionally modulate dopamine neurons is crucial for the development of better therapeutic strategies against dopamine-related disorders. Phospholipase Cγ1 (PLCγ1) is a key enzyme in intracellular signaling that regulates diverse neuronal functions in the brain. It was proposed that PLCγ1 is implicated in the development of dopaminergic neurons, while the physiological function of PLCγ1 remains to be determined. In this study, we investigated the physiological role of PLCγ1, one of the key effector enzymes in intracellular signaling, in regulating dopaminergic function in vivo. We found that cell type-specific deletion of PLCγ1 does not adversely affect the development and cellular morphology of midbrain dopamine neurons but does facilitate dopamine release from dopaminergic axon terminals in the striatum. The enhancement of dopamine release was accompanied by increased colocalization of vesicular monoamine transporter 2 (VMAT2) at dopaminergic axon terminals. Notably, dopamine neuron-specific knockout of PLCγ1 also led to heightened expression and colocalization of synapsin III, which controls the trafficking of synaptic vesicles. Furthermore, the knockdown of VMAT2 and synapsin III in dopamine neurons resulted in a significant attenuation of dopamine release, while this attenuation was less severe in PLCγ1 cKO mice. Our findings suggest that PLCγ1 in dopamine neurons could critically modulate dopamine release at axon terminals by directly or indirectly interacting with synaptic machinery, including VMAT2 and synapsin III.
Comparative transcriptomic analysis of social hornets Vespa crabro and Vespa analis
Kyungjae Andrew Yoon,Kyungmun Kim,Hyo-min Ah,Ki-Gyoung Kim,Young Ho Koh,Young Ho Koh,Si Hyeock Lee 한국응용곤충학회 2015 한국응용곤충학회 학술대회논문집 Vol.2015 No.10
The hornets Vespa crabro and V. analis are widely distributed in Asia and are known to be aggressive when disturbed, resulting in frequent stinging accidents. To investigate the differences in venom properties and toxicities between these two hornets, the transcriptomic profiles of venom glands, in conjunction with the venom components, were analyzed and compared. A total of 35 venom-specific genes were identified in both venom gland transcriptomes, but their transcriptional profiles were different between V. crabro and V. analis. In addition, the major venom components were identified and confirmed by mass spectroscopy. Prepromastoparan, vespid chemotactic precursor and vespakinin were the top three genes most prevalently transcribed in the venom gland of V. crabro, and their transcription rates were 112-, 16- and 161-fold higher, respectively, compared with those in V. analis, as judged by FPKM values. In the venom gland of V. analis, however, vespid chemotactic precursor was the most abundantly transcribed gene, followed by premastoparan and vespakinin. In general, most major venom genes were more abundantly expressed in V. crabro, whereas some minor venom genes exhibited higher transcription rates in V. analis, including muscle LIM protein, troponin, paramyosin, calponin, etc. Our findings reveal that the overall venom components of V. crabro and V. analis are similar, but that their expression profiles and levels are considerably different. The comparison of venom gland transcriptomes suggests that V. crabro likely produces venom with more highly enriched major venom components, which has potentially higher toxicity compared with V. analis venom.
Kim, Seulah,Shin, Seulmee,Hyun, Bobae,Kong, Hyunseok,Han, Shinha,Lee, Aeri,Lee, Seungjeong,Kim, Kyungjae 대한면역학회 2012 Immune Network Vol.12 No.5
Dioscoreae Rhizome (DR) has been used in traditional medicine to treat numerous diseases and is reported to have anti-diabetes and anti-tumor activities. To identify a bioactive traditional medicine with anti-inflammatory activity of a water extract of DR (EDR), we determined the mRNA and protein levels of proinflammatory cytokines in macrophages through RT-PCR and western blot analysis and performed a FACS analysis for measuring surface molecules. EDR dose-dependently decreased the production of NO and pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and PGE<sub>2</sub>, as well as mRNA levels of iNOS, COX-2, and pro-inflammatory cytokines, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as B7-1 and B7-2 was also reduced by EDR. Furthermore, activation of the nuclear transcription factor, NF-κB , but not that of IL-4 and IL-10, in macrophages was inhibited by EDR. These results show that EDR decreased pro-inflammatory cytokines via inhibition of NF-κB -dependent inflammatory protein level, suggesting that EDR could be a useful immunomodulatory agent for treating immunological diseases.
Kim, Kyungmun,Kim, Sang Hyeon,Yoon, Kyungjae Andrew,Cho, Yun Sang,Yoo, Mi-Sun,Lee, Si Hyeock 한국응용곤충학회 2018 Journal of Asia-Pacific Entomology Vol.2 No.1
<P><B>Abstract</B></P> <P>The small hive beetle (SHB), <I>Aethina tumida</I>, is an invasive pest species in most Northern Hemisphere countries, including Korea. SHB causes serious damage to apiaries by destroying overwintering honey bee colonies. To obtain basic information for efficient management of SHB, genes encoding conventional insecticide targets, specifically the voltage-sensitive sodium channel α-subunit (VSSC) and acetylcholinesterase (AChE), and RNA interference (RNAi)-related components were annotated and characterized following analysis of transcriptomes of adults and larvae. A single VSSC gene was identified but no apparent mutations associated with pyrethroid resistance were detected. Genes encoding two AChEs (AtAChE1 and AtAChE2) were identified from the SHB transcriptome. No apparent mutations associated with resistance to organophosphorus and carbamate insecticides were identified in the AtAChE1 gene, whereas the S238G mutation, originally identified from the Colorado potato beetle, was detected in the AtAChE2 gene. Native polyacrylamide electrophoresis in conjunction with western blotting revealed that AtAChE1 was the main catalytic enzyme and therefore a toxicologically more relevant target. AtAChE1 was determined to exist in both membrane-anchored and soluble forms. The main components of RNA interference (RNAi) were identified, suggesting that RNAi is likely functional in SHB and an RNAi-based approach is a feasible alternative control measure.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Transcriptome of small hive beetle (<I>Aethina tumida</I>) was analyzed and annotated. </LI> <LI> Insecticide target (<I>Atvssc</I> and <I>Atace</I>) and RNAi-related genes were characterized. </LI> <LI> Of two <I>Atace</I> genes (<I>Atace1</I> and <I>Atace2</I>)<I>, Atace1</I> was determined to encode the major enzyme. </LI> <LI> No apparent mutations associated with insecticide resistance were detected in either <I>Atvssc</I> or <I>Atace1</I>. </LI> <LI> Two additional RNAi-related components (Hen1 and loqs) were newly identified. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>