• Title/Summary/Keyword: host factors

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Regulation of Tumor Neceosis Factor-${\alpha}$ Receptors and Signal Transduction Pathways

  • Han, Hyung-Mee
    • Toxicological Research
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    • v.8 no.2
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    • pp.343-357
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    • 1992
  • Tumor necrosis factor-${\alpha}$(TNF), a polypeptide hormone secreted primarily by activated macrophages, was originally identified on the basis of its ability to cause hemorrhagic necrosis and tumor regression in vivo. Subsequently, TNF has been shown to be an important component of the host responses to infection and cancer and may mediate the wasting syndrome known as cachexia. These systemic actions of TNF are reflected in its diverse effects on target cells in vitro. TNF initiates its diverse cellular actions by binding to specific cell surface receptors. Although TNF receptors have been identified on most of animal cells, regulation of these receptors and the mechanisms which transduce TNF receptor binding into cellular responses are not well understood. Therefore, in the present study, the mechanisms how TNF receptors are being regulated and how TNF receptor binding is being transduced into cellular responses were investigated in rat liver plasma membranes (PM) and ME-180 human cervical carcinoma cell lines. $^{125}I$-TNF bound to high ($K_d=1.51{\pm}0.35nM$)affinity receptors in rat liver PM. Solubilization of PM with 1% Triton X-100 increased both high affinity (from $0.33{\pm}0.04\;to\;1.67{\pm}0.05$ pmoles/mg protein) and low affinity (from $1.92{\pm}0.16\;to\;7.57{\pm}0.50$ pmoles/mg protein) TNF binding without affecting the affinities for TNF, suggesting the presence of a large latent pool of TNF receptors. Affinity labeling of receptors whether from PM or solubilized PM resulted in cross-linking of $^{125}I$-TNF into $M_r$ 130 kDa, 90 kDa and 66kDa complexes. Thus, the properties of the latent TNF receptors were similar to those initially accessible to TNF. To determine if exposure of latent receptors is regulated by TNF, $^{125}I$-TNF binding to control and TNF-pretreated membranes were assayed. Specific binding was increased by pretreatment with TNF (P<0.05), demonstrating that hepatic PM contains latent TNF receptors whose exposure is promoted by TNF. Homologous up-regulation of TNF receptors may, in part, be responsible for sustained hepatic responsiveness during chronic exposure to TNF. As a next step, the post-receptor events induced by TNF were examined. Although the signal transduction pathways for TNF have not been delineated clearly, the actions of many other hormones are mediated by the reversible phosphorylation of specific enzymes or target proteins. The present study demonstrated that TNF induces phosphorylation of 28 kDa protein (p28). Two dimensional soidum dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) resolved the 28kDa phosphoprotein into two isoforms having pIs of 6.2 and 6.1. The pIs and relative molecular weight of p28 were consistent with those of a previously characterized mRNA cap binding protein. mRNA cap binding proteins are a class of translation initiation factors that recognize the 7-methylguanosine cap structure found on the 5' end of eukaryotic mRNAs. In vitro, these proteins are defined by their specific elution from affinity columns composed of 7-methylguanosine 5'-triphosphate($m^7$GTP)-Sepharose. Affinity purification of mRNA cap binding proteins from control and TNF treated ME-180 cells proved that TNF rapidly stimulates phosphorylation of an mRNA cap binding protein. Phosphorylation occurred in several cell types that are important in vitro models of TNF action. The mRNA cap binding protein phosphorylated in response to TNF treatment was purifice, sequenced, and identified as the proto-oncogene product eukaryotic initiation factor-4E(eIF-4E). These data show that phosphorylation of a key component of the cellular translational machinery is a common early event in the diverse cellular actions of TNF.

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Seasonal Changes in Colonization and Spore Density of Arbuscular-Mycorrhizae in Citrus Groves (감귤뿌리에서의 Arbuscular-Mycorrhizae 형성과 감귤원 토양중 포자밀도의 계절적 변화)

  • Kim, Sang-Youb;Oh, Hyun-Woo;Moon, Doo-Khil;Han, Hae-Ryong;Chung, Jong-Bae
    • Korean Journal of Environmental Agriculture
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    • v.17 no.2
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    • pp.174-181
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    • 1998
  • In four citrus grow of Satsuma mandarin (rootstock of trifoliate orange) including two grove of organical management and two groves of conventional management, spores of arbuscular mycorrhizal(AM) fungi were identified and seasonal changes in spore density in soils and AM colonization of citrus roots were investigated. AM colonization in weeds found in the groves were also examined. Three species of Glomus (G.deserticola, G. vesiculiferum, G. rubiforme ) and one unknown species of Acaulospora were observed in all of the groves. Annual mean density of AM fungal spores were in the range of 10,000${\sim}$40,000 per 100g soil with more spores in the organically-managed groves. The least spores were observed in December in all groves, and the most spores in April in the organically-managed groves while in February or April in the conventionally- managed. Annual mean AM colonization more 27% of citrus root were observed in the organically-managed with the high peaks in April and October and the minimum in August, while mean colonization less than 15% in the conventionally-managed with the peak in February and the minimum in different times depending on groves and years. AM colonization corresponded to a sigmoidal curve consisting of a laf phase during winter and a subsequent increase in spring, then succeeded by a maximum, and then a decrease at the end of vegetation. Fungal spore density and AM colonization showed a parallel pattern during the sample period. The seasonality appeared to be related more to the phenology of the plant than to the soil factors. Generally more spore density and AM colonization were found in organically managed groves. AM colonization was not correlated with available P and organic matter content in soil in this field investigation. Among sixteen weed species found in the groves, Astrogalus sinicus of Leguminosae, Portulaca oleracea of Portulacaceae showed high colonization in all groves and they can be considered as a source of inoculumn and host plants for propagation of AM fungi.

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Polymorphisms of HLA-DRB1 and -DQB1 Genes in Korean Patients with Pulmonary Tuberculosis (한국인 폐결핵 환자에서 HLA-DRB1 및 -DQB1 유전자의 다형성에 관한 연구)

  • Park, Myoung Hee;Song, Eun Young;Kwon, Sung Youn;Park, He Jin;Han, Sung Koo;Shim, Young Soo
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.4
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    • pp.367-377
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    • 2003
  • Background : It is well known that only 10% of those infected with Mycobacterium tuberculosis actually develop clinical disease, indicating the existence of host genetic factors regulating disease expression. In this study, we investigated HLA-DRB1 and -DQB1 gene polymorphisms in Korean patients with pulmonary tuberculosis (PTB). Methods : HLA-DRB1 and -DQB1 gene polymorphisms were investigated in 67 PTB patients without previous treatment history, 38 drug-sensitive (DS) and 29 multidrug-resistant (MDR) cases, and 200 healthy controls. HLA-DRB1 typing was done using reverse SSO (sequence specific oligonucleotide) and PCR-SSCP (single strand conformational polymorphism) methods and DQB1 typing was done using PCR-RFLP (restriction fragment length polymorphism), PCR-SSCP and PCR-SSP (sequence specific primer) methods. Results : Among the PTB patients, MDR-TB cases showed frequencies of DRB1*0701 and *08032 increased by about two-fold compared to those of normal controls, and likewise for their associated DQB1 alleles, DQB1*0202 and *0601 (15.5% vs. 34.5%, p=0.01). The frequency of HLA-DQB1*0609 was significantly increased in PTB patients (4.0% vs. 14.9%, p=0.004), showing similar increases in both DS and MDR cases. There was also an association of HLA alleles with the clinical severity of the disease according to the extent of lung lesion. Significantly increased frequencies of DRB1*08032 (4.2% vs. 32.6%, p=0.007) and DQB1*0601 (12.5% vs. 34.9%, p=0.047) were observed in more advanced (moderately & far advanced/DS and far advanced/MDR), compared with less advanced (minimal/DS and moderately advanced/MDR) lung lesions. Although DRB1*0701, DQB1*0202 and DQB1*0609 showed significant increases in different subsets of the disease, these HLA alleles did not show consistent association with disease severity. Conclusion : HLA-DRB1*08032 and DQB1*0601 alleles were associated with genetic susceptibility to MDR-TB in Korean patients, and also with disease severity and progression of PTB.

Endocrine dysfunction after bone marrow transplantation during childhood and adolescence (소아 및 청소년기에서 골수이식 후에 발생할 수 있는 내분비 기능 부전)

  • Jin, Hye Young;Choi, Jin-Ho;Im, Ho-Joon;Seo, Jong-Jin;Moon, Hyung-Nam;Yoo, Han-Wook
    • Clinical and Experimental Pediatrics
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    • v.53 no.3
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    • pp.420-427
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    • 2010
  • Purpose : Several complications can occur in patients who received bone marrow transplantation (BMT) during childhood and adolescence. This study aims to investigate endocrine dysfunctions after BMT so that better care can be provided to care for long-term survivors of BMT. Methods : One hundred patients (61 males, 39 females) were included in this study. Clinical parameters such as initial diagnosis, age at BMT, conditioning regimen, presence of graft-versus-host disease (GVHD), growth pattern, thyroid function, and pubertal status were retrospectively reviewed to evaluate risk factors associated with endocrine dysfunction. Results : Height standard deviation score (SDS) at BMT, after 1 year of BMT, and at the last visit were $0.08{\pm}1.04$, $-0.09{\pm}1.02$, and $-0.27{\pm}1.18$, respectively (P =0.001). Height SDS significantly decreased in patients who received total body irradiation (TBI) (P =0.017). One of the patients who received TBI demonstrated growth hormone deficiency. Thirty (31.9%) of 94 patients had compensated hypothyroidism. Incidence of compensated hypothyroidism was higher among those who had GVHD (odds ratio 2.82, P =0.025). Of the 32 patients (17 males, 15 females) who were over 14 years in male and 13 years in female at the last visit, 16 (3 males, 13 females) had increased luteinizing hormone (LH) or follicle-stimulating hormone (FSH). Abnormal elevation of LH or FSH was more common in females (odds ratio 30.3, P =0.001). Conclusion : The most common endocrine dysfunction was ovarian insufficiency. Regular check-up for endocrine function needs to be required due to high incidence of endocrine dysfunction in patients with BMT.

A Phase II Trial of Combination Chemotherapy with Cisplatin & Etoposide in Small Cell Lung Cancer (소세포폐암에 대한 Cisplatin과 Etoposide(PVP) 복합화학요법의 효과)

  • Cheon, Eun-Mee;Kim, Hyung-Gun;Son, Tae-Young;Yuh, Young-Jin;Lee, Sang-Goo;Lee, Choon-Taek;Kim, Young-Hwan;Lee, Jhin-Oh;Kang, Tae-Woong
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.6
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    • pp.632-643
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    • 1994
  • Background: The objective responses of cisplatin and etoposide (PVP) combination chemotherapy as second-line therapy following CAV was high (40~50%) and, in several reports, PVP yields survival results that are at least as good as those obtained with cyclophosphamide or doxorubicin-based regimens and with less host-related toxicity in chemotherapy-naive patients. We conducted a phase II study to evaluate the effect of a combination of cisplatin and etoposide as a fitst-line therapy in patients with small cell lung cancer. Methods: Sixty-one previously untreated small cell lung cancer patients with measurable lesion (s) received cisplatin(30 $mg/m^2$ IV, day 1~3) and etoposide(100 $mg/m^2$ IV, day 1~3). In patients with limited disease, after completion of 6 cycles of PVP chemotherapy, chest and prophylatic brain irradiation was performed in case of complete responder, chest irradiation on1y in partial responder. Results: 1) Of 55 evaluable patients, 13(24%) had a complete response and 29(53%) had a partial response. 2) The median survival time was 55.8 weeks for all patients(N=55), 61.1 weeks for limited disease(N=31), 51.3 weeks for extensive disease(N=24). 3) The response duration was 29.1 weeks for responders(N=42). 4) There was no significant prognostic factors influencing response rates. 5) The toxicity was tolerable and there was no treatment-related deaths. Conclusion: The PVP combination chemotherapy as a first-line therapy was effective and well-tolerated in patients with small cell lung cancer.

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The Prognostic Indicies of Pneumocystis Carinii Pneumonia in Immunocompromised Patients other than Acquired Immune Deficiency Syndrome (비 AIDS 면역 결핍 환자들에서 발생한 주폐포자충 폐렴의 예후인자)

  • Park, Wann;Kim, Yoo-Kyum;Lee, Jin-Seong;Ahn, Jong-Jun;Hong, Sang-Bum;Shim, Tae-Sun;Lim, Chae-Man;Lee, Sang-Do;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong;Koh, Youn-Suck
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.805-812
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    • 1998
  • Background: Among the variety of opportunistic infections, pneumonia comprises the major morbidity in immunocompromised patients. Pneumocystis carnii pneumonia (PCP) and cytomegalovirus (CMV) pneumonia are common infectious illness of immunocompromised hosts. Although there are many reports regarding to the co-infection of PCP and CMV diagnosed by bronchoalveolar lavage (BAL) fluid examination, the effects of CMV co-infection on the outcome of PCP is still controversial. The purpose of this investigation is to evaluate the effects of CMV detected by BAL fluid examination on the clinical course of PCP in the immunocompromised patients other than human immunodeficiency virus infection. Method: Ten patients with PCP were enrolled and retrospective analysis of their medical records were done. HIV infected persons were excluded. The PCP was diagnosed by BAL fluid examination with Calcofluor-White staining. CMV was detected in BAL fluid by Shell-vial culture system. Chest radiographic findings were reviewed. We used Fisher's exact test and Mann-Whitney U test for statistical analysis of data. Results: The underlying disorders of patients were idiopathic pulmonary fibrosis (n=1), renal transplantation (n=4), necrotizing vasculitis (n=l), systemic lupus erythematosus (n=1), brain tumor (n=1), chronic myelogenous leukemia (n=1), unidentified (n=1). There were no difference in clinical course, APACHE III score, arterial blood gas analysis, white blood cell count, lymphocyte count, serum albumin concentration, chest radiographic findings and mortality between patients with PCP alone (n=4) and those with CMV co-infection (n=6). Univariate analysis regarding to the factors that associated with mortality of PCP were revealed that the application of mechanical ventilation (p=0.028), the level of APACHE III score (p=0.018) and serum albumin concentration (p=0.048) were related to the mortality of patients with PCP. Conclusion: The clinical course of PCP patients co-infected by CMV were not different from PCP only patients. Instead, accompanied respiratory failure, high APACHE III score and poor nutritional status were associated with poor outcome of PCP.

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Comparison of pathogen detection from wild and cultured olive flounder, red sea bream, black sea bream and black rockfish in the coastal area of Korea in 2010 (2010년 한국 연근해 자연산과 양식산 넙치, 참돔, 감성돔, 조피볼락의 병원체 비교)

  • Park, Myoung Ae;Do, Jeung-Wan;Kim, Myoung Sug;Kim, Seok-Ryel;Kwon, Mun-Gyeong;Seo, Jung Soo;Song, Junyoung;Choi, Hye-Sung
    • Journal of fish pathology
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    • v.25 no.3
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    • pp.263-270
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    • 2012
  • This study surveyed for the prevalence of parasites, bacteria and viruses in four fish species, olive flounder (Paralichthys olivaceus), red sea bream (Pagrus major), black sea bream (Acathopagrus schlegeli) and black rockfish (Sebastes schlegeli) in 2010. The survey was aimed to compare the pathogens detected from wild and cultured fish for an epidemiological study. Anisakis sp. was predominantly detected from wild olive flounder and red sea bream (58.6% and 41.7% respectively), but not from the cultured fishes, suggesting anisakid infection is rare in cultured fish. The wild fish get in contact with the anisakids through their prey such as small fishes or crustaceans which carry the anisakids; whereas the cultured fish are fed with formulated feed, free of anisakids. Bacterial detection rates from the wild fishes examined in the study were lower than those of cultured fishes. Vibrio sp. dominated among detected bacterial population in cultured olive flounder (18%). Since vibriosis is known as a secondary infection caused by other stressful factors such as parasitic infections, handling and chemical treatment, it seems that cultured olive flounder are exposed to stressful environment. Viruses diagnosed in the study showed difference in distribution between wild and cultured fishes; hirame rhabdovirus (HRV) (0.1%) and lymphocystis disease virus (LCDV) (3.9%) were detected in the cultured olive flounder, but not in the wild fish, and marine birnavirus (MBV) (1.7%) and red sea bream iridovirus (RSIV) (3.2%) were detected from the wild and cultured red sea bream, respectively. From the survey conducted, it can be concluded that even though some pathogens (Trichodina sp., Microcotyle sp., etc.) are detected from both the wild and cultured fish, pathogens such as Anisakis sp., Vibrio sp. and LCDV showed difference in distribution in the wild and cultured host of same fish species and this can be attributed to their environmental condition and feeding.

Effects of Enterococcus faecalis sonicated extracts on IL-2, IL-4 and TGF-β1 production from human lymphocytes (Enterococcus faecalis 추출물이 임파구의 IL-2, IL-4, TGF-β1 분비에 미치는 영향에 관한 연구)

  • Kim, Hyeon-Sik;Lee, Woo-Cheol;Jang, Seok-Woo;Shon, Wan-Jun;Lee, Sang-Takg;Kim, Cheol-Ho;Lim, Sung-Sam
    • Restorative Dentistry and Endodontics
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    • v.30 no.1
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    • pp.1-6
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    • 2005
  • In order to examine the immunoresponse of host cells to Enterococcus faecalis, this in vitro study monitored the production of Interleukin-2 (IL-2), Interleukin-4 (IL-4) and Transforming growth factor-$\beta1\;(TGF-\beta1)$ in human lymphocytes. Lymphocytes were activated with PHA in the presence or abscence of sonicated extracts of E. Faecalis (SEF) and further incubated for 72 hours. The level of each cytokine was measured by ELISA. Data were analyzed with Kruskal-Wallis test and Mann-Whitney U test (P < 0.05). PHA-activated group did exhibit higher level of IL-2 and IL-4 than untreated control group. The levels of expression of both cytokines were significantly decreased following the treatment of high (25 ${\mu}g/ml$) and medium concentration (12.5 ${\mu}g/ml$)) of SEF (P > 0.05) than those of PHA activated group. But low concentration (5 ${\mu}g/ml$)) of SEF showed th similar level of IL-2 and IL-4 production as those of PHA activated group. $TGF-\beta1$ was unaffected by SEF treatment. These results suggested that E. faecalis may suppress IL-2 and IL-4 production by lymphocytes and this could be one of possible factors why E. faecalis are found frequently in the teeth with failed endodontic treatment.

Studies on the Development of Acid Tolerant and Superior Nitrogen Fixation Symbionts for Pasture on Hilly Land -II. Selection of Acid Tolerant R. meliloti in virto and Inoculation Effect in Soils (야산(野山) 목초지용(牧草地用) 내산성(耐酸性) 우수(優秀) 질소고정균주(窒素固定菌株) 개발(開發) -II. 내산성(耐酸性) R. meliloti 의 기내선발(器內選拔) 및 토양(土壤) 접종효과(接種效果))

  • Kang, Ui-Gum;Choi, Ju-Hyeon;Cho, Kang-Jin;Jung, Yeun-Tae;Cho, Moo-Je
    • Korean Journal of Soil Science and Fertilizer
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    • v.22 no.1
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    • pp.72-77
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    • 1989
  • A study was conducted to obtain acid tolerant and superior Rhizobium meliloti strain for alfalfa on hilly acid soils. With host plant, eight isolates of R, meliloti selected in the vicinity of Milyang were evaluated for their ability to establish symbiotic effectiveness in acidified tube culture medium and vermiculite pot with different urea levels. Among isolates "YA03" was characterized for the ability to manifest to acid tolerance in three different soils of which pH were 5.0, 6.0, and 7.5. The results obtained were summarized as follows: 1. Of eight isolates "YA03" and "YA09" performed nodule in the tube medium of pH5.0, and in the symbiotic effectiveness YA03 was superior to others. 2. Alfalfa growth and $N_2-fixing$ activity by the inoculation of "YA03" isolate were better than others at the level of urea 1.25mM as well as nonurea. 3. Application of urea with inoculation of "YA03" islate to alfalfa was one of the effective factors for symbiotic effectiveness. 4. In infertile soil of pH5.0 inoculation of R. meliloti "YA03" to alfalfa caused the increase of shoot dry matter of 320% as compared to the control, and the total amount of yield was 131% as much yield in moderate fertile soil of pH7.5. Finally R. meliloti "YA03" isolate was selected as an acid tolerant strain.

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Molecular Characterization and Expression Analysis of Clathrin-Associated Adaptor Protein 3-δ Subunit 2 (AP3S2) in Chicken

  • Oh, Jae-Don;Bigirwa, Godfrey;Lee, Seokhyun;Song, Ki-Duk
    • Korean Journal of Poultry Science
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    • v.46 no.1
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    • pp.31-37
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    • 2019
  • A chicken clathrin-associated adaptor protein $3-{\delta}$ subunit 2 (AP3S2) is a subunit of AP3, which is involved in cargo protein trafficking to target membrane with clathrin-coated vesicles. AP3S2 may play a role in virus entry into host cells through clathrin-dependent endocytosis. AP3S2 is also known to participate in metabolic disease developments of progressions, such as liver fibrosis with hepatitis C virus infection and type 2 diabetes mellitus. Chicken AP3S2 (chAP3S2) gene was originally identified as one of the differentially expressed genes (DEGs) in chicken kidney which was fed with different calcium doses. This study aims to characterize the molecular characteristics, gene expression patterns, and transcriptional regulation of chAP3S2 in response to the stimulation of Toll-like receptor 3 (TLR3) to understand the involvement of chAP3S2 in metabolic disease in chicken. As a result, the structure prediction of chAP3S2 gene revealed that the gene is highly conserved among AP3S2 orthologs from other species. Evolutionarily, it was suggested that chAP3S2 is relatively closely related to zebrafish, and fairly far from mammal AP3S2. The transcriptional profile revealed that chAP3S2 gene was highly expressed in chicken lung and spleen tissues, and under the stimulation of poly (I:C), the chAP3S2 expression was down-regulated in DF-1 cells (P<0.05). However, the presence of the transcriptional inhibitors, BAY 11-7085 (Bay) as an inhibitor for nuclear factor ${\kappa}B$ ($NF{\kappa}B$) or Tanshinone IIA (Tan-II) as an inhibitor for activated protein 1 (AP-1), did not affect the expressional level of chAP3S2, suggesting that these transcription factors might be dispensable for TLR3 mediated repression. These results suggest that chAP3S2 gene may play a significant role against viral infection and be involved in TLR3 signaling pathway. Further study about the transcriptional regulation of chAP3S2 in TLR3 pathways and the mechanism of chAP3S2 upon virus entry shall be needed.