Cytokine-cytokine receptor interactions in the highly pathogenic avian influenza H5N1 virus-infected lungs of genetically disparate Ri chicken lines

부 티 하오,Hong Yeojin,츠엉앵득,Lee Jiae,Lee Sooyeon,송기덕,Cha Jihye,Dang Hoang Vu,Tran Ha Thi Thanh,Lillehoj,Hyun S.,홍영호 아세아·태평양축산학회 2022 Animal Bioscience Vol.35 No.3

Objective: The highly pathogenic avian influenza virus (HPAIV) is a threat to the poultry industry as well as the economy and remains a potential source of pandemic infection in humans. Antiviral genes are considered a potential factor for HPAIV resistance. Therefore, in this study, we investigated gene expression related to cytokine-cytokine receptor interactions by comparing resistant and susceptible Ri chicken lines for avian influenza virus infection. Methods: Ri chickens of resistant (Mx/A; BF2/B21) and susceptible (Mx/G; BF2/B13) lines were selected by genotyping the Mx dynamin like GTPase (Mx) and major histocompatibility complex class I antigen BF2 genes. These chickens were then infected with influenza A virus subtype H5N1, and their lung tissues were collected for RNA sequencing. Results: In total, 972 differentially expressed genes (DEGs) were observed between resistant and susceptible Ri chickens, according to the gene ontology and Kyoto encyclopedia of genes and genomes pathways. In particular, DEGs associated with cytokine-cytokine receptor interactions were most abundant. The expression levels of cytokines (interleukin-1β [IL-1β], IL-6, IL-8, and IL-18), chemokines (C-C Motif chemokine ligand 4 [CCL4] and CCL17), interferons (IFN-γ), and IFN-stimulated genes (Mx1, CCL19, 2’-5’-oligoadenylate synthaselike, and protein kinase R) were higher in H5N1-resistant chickens than in H5N1-susceptible chickens. Conclusion: Resistant chickens show stronger immune responses and antiviral activity (cytokines, chemokines, and IFN-stimulated genes) than those of susceptible chickens against HPAIV infection. Objective: The highly pathogenic avian influenza virus (HPAIV) is a threat to the poultry industry as well as the economy and remains a potential source of pandemic infection in humans. Antiviral genes are considered a potential factor for HPAIV resistance. Therefore, in this study, we investigated gene expression related to cytokine-cytokine receptor interactions by comparing resistant and susceptible Ri chicken lines for avian influenza virus infection.Methods: Ri chickens of resistant (Mx/A; BF2/B21) and susceptible (Mx/G; BF2/B13) lines were selected by genotyping the Mx dynamin like GTPase (Mx) and major histocompatibility complex class I antigen BF2 genes. These chickens were then infected with influenza A virus subtype H5N1, and their lung tissues were collected for RNA sequencing.Results: In total, 972 differentially expressed genes (DEGs) were observed between resistant and susceptible Ri chickens, according to the gene ontology and Kyoto encyclopedia of genes and genomes pathways. In particular, DEGs associated with cytokine-cytokine receptor interactions were most abundant. The expression levels of cytokines (interleukin-1β [IL-1β], IL-6, IL-8, and IL-18), chemokines (C-C Motif chemokine ligand 4 [CCL4] and CCL17), interferons (IFN-γ), and IFN-stimulated genes (Mx1, CCL19, 2’-5’-oligoadenylate synthaselike, and protein kinase R) were higher in H5N1-resistant chickens than in H5N1-susceptible chickens.Conclusion: Resistant chickens show stronger immune responses and antiviral activity (cytokines, chemokines, and IFN-stimulated genes) than those of susceptible chickens against HPAIV infection.

왼온엉덩동맥 허혈 후 재관류 시간경과에 따른 생쥐의 혈청 내 친염증성 cytokine의 변화

박경신(Kyung shin Park),김성재(Sung Jae Kim),서윤경(Younkyoung Seo) 대한체질인류학회 2016 해부·생물인류학 (Anat Biol Anthropol) Vol.29 No.1

허혈 재관류 손상은 허혈이 이루어진 후 재관류되면서 일어난다. 허혈 재관류 손상의 주요 원인은 활성산소기와 활성화된 면역세포가 분비하는 cytokine이다. Cytokine은 감염이나 면역반응, 염증 등의 반응을 조절하는 세포 사이의 신호전달물질로, 염증반응을 증가시키는 것을 친염증성 cytokine이라 한다. 본 실험에서 저자들은 허혈후 재관류 경과에 따른 친염증성 cytokine인 IL-1α, IL-1β, IL-2, IL-3, IL-5, IL-6, eotaxin, MCP-1, MDC, MIP-1α, RANTES, TARC, IFNγ의 변화를 알아보았다. 12주령의 수컷 생쥐를 이용하여 정상대조군과 2시간 허혈군, 4시간 허혈군, 6시간 허혈군으로 구분하였고, 총 96마리의 생쥐를 사용하였다. 허혈처치는 왼온엉덩동맥을 혈관집게를 이용하여 차단하였고, 각 허혈군은 재관류 경과에 따라 0시간, 2시간, 4시간, 8시간, 16시간으로 재분류하였다. 재관류 시간에 따라 생쥐를 마취시킨 후 심장에서 혈액을 채취하였다. 혈청을 분리한 후 ELISA 분석방법을 이용하여 IL-1α, IL-1β, IL-2, IL-3, IL-5, IL-6, eotaxin, MCP-1, MDC, MIP-1α, RANTES, TARC, IFNγ의 농도를 측정하여 다음과 같은 결과를 얻었다. 13개의 cytokine 농도는 허혈시간에 따라 그리고 재관류 시간에 따라 유의한 차이가 있었다. 허혈 2시간군에서 IL-1α와 IL-3는 정상대조군보다 유의성 있게 증가되었고, 재관류 후 MIP-1α를 제외한 모든 cytokine들은 증가하였으며, MCP-1과 TARC은 재관류 16시간에 가장 높은 농도로 관찰되었다. 허혈 4시간군에서 TARC만이 정상대조군보다 유의성 있게 증가되었으며, 재관류 후 모든 cytokine들은 재관류 4시간 이후에 감소하는 경향으로 관찰되었다. 허혈 6시간군에서 IL-2, IL-3, MCP-1, TARC은 정상대조군보다 유의성 있게 증가되었고, 재관류 16시간에 IL-3와 MCP-1이 유의성 있게 증가되었다. 이상의 결과를 종합하면, 허혈은 친염증성 cytokine을 정상대조군보다 증가시키는 것을 알 수 있었고, 특히 2시간과 6시간 허혈군에서 관찰된 IL-1α, IL-3, MCP-1, TARC은 재관류 후기까지 비교적 높은 농도로 유지되는 것을 알 수 있었다. Ischemia-reperfusion injury arises from the restoration of blood supply after ischemia. Both reactive oxygen species and various cytokines produced by activated immune cells are the primary causal risk factors for ischemic injury. Cytokines are intercellular signaling substances for regulating any infection, immune reactions and inflammation, and pro-inflammatory cytokines adversely affect any diseases through an increase in inflammatory reaction. This study was conducted to investigate whether the periods of reperfusion after ischemia result in any changes of pro-inflammatory cytokines in the serum, including IL-1α, IL-1β, IL-2, IL-3, IL-5, IL-6, Eotaxin, MCP-1, MDC, MIP-1α, RANTES, TARC, IFNδ. A total of 96 male mice aged at 12 weeks was used in this study, and the groups of ischemia were divided into the following three different groups: 2-hour, 4-hour, and 6-hour ischemia groups. For the object of ischemic injury, the left common iliac artery was clamped by vascular clamp, each ischemia group was subdivided into 5 different groups according to the periods of reperfusion: 0-, 2-, 4-, 8-, and 16-hour reperfusion time. Blood samples after general anesthesia were collected from the mice hearts, and the serum was separated from them. The concentration of pro-inflammatory cytokines (IL-1α, IL-1β, IL-2, IL-3, IL-5, IL-6, Eotaxin, MCP-1, MDC, MIP-1α, RANTES, TARC, IFNδ) in the serum was measured by ELISA, and the following results were acquired. The concentrations of the 13 pro-inflammatory cytokines were significantly different in accordance with the periods of ischemia and the reperfusion time. In 2-hour ischemia group, IL-1α and IL-3 were increaed compared to normal control group, and 12 cytokines were increased followed by reperfusion except for MIP-1α. MCP- 1 and TARC were expressed as the highest concentration in the 16-hour reperfusion time. In 4-hour ischemia group, TARC was significant differences with normal control group, and the concentration of 13 cytokines were decreased after 4-hour reperfusion time. In 6-hour ischemia group, IL-2, IL-3, MCP-1 and TARC were increased, compared to normal control group, and IL-3 and MCP-1 were increased in 16-hour reperfusion time. To sum up, ischemia increased the pro-inflammatory cytokines compared to normal control group and in the 2-hour and 6-hour ischemia groups, IL-1α, IL-3, MCP-1 and TARC were increased until the late reperfusion time.

인체 대장상피세포에 대한 이질 아메바의 접촉 차단이 친염증성 Cytokine 유전자 발현 유도에 미치는 영향

김정목,정현채,이경미,진영주,김영전,송인성,김정룡 大韓消化器病學會 1997 大韓消化器病學會誌 Vol.30 No.2

HCC : PE-056 ; Change of cytokine profile following transarterial chemotherapy in patients with hepatocellular carcinoma

( Min Ju Kim ),( Jeong Won Jang ),( Jung Hyun Kwon ),( Chan Ran You ),( Nam Ik Han ),( Chang Don Lee ),( Hyun Suk Jung ),( Dong Wook Jekarl ),( Seung Ok Lee ),( Kyu Won Chung ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background: Although alterations in cytokine profile after therapy can affect the outcome and prognosis of cancer patients, there are no comprehensive data on multiple cytokine profiles during transarterial chemotherapy (TACE). Methods: Cytometric bead immunoassay was used to simultaneously measure 13 cytokines (interleukin [IL]-12p70, IFN-γ, IL-17A, IL-2, IL-10, IL-9, IL-22, IL-6, IL-13, IL-4, IL-5, IL-1β, and TNF-α) in the sera of 83 patients with hepatocellular carcinoma (HCC) and 18 healthy controls. Those cytokines were serially monitored at baseline, day 3, day 7, and 2 months after TACE in 63 evaluable patients. Results: Serum levels of IL-17A and IL-5 were higher in HCC patients than healthy controls, whereas IL-22 and IL-1β levels were lower in HCC patients. Although the overall patterns of cytokine changes were diverse at each set date, certain cytokines specifically increased after TACE, with the early-phase increase in IL-6 and IL-22 levels and late-phase increase in IL-4, IL-6, and IL-10 levels. With relatively minor changes of cytokines after TACE, Childs B/C group had higher IL-6 and lower IL-22 levels than Childs A group. Patients with larger tumors (>5 cm) had higher IL-6 levels at baseline and showed a transient but significant early-phase increase in IL-6 levels as well as late-phase increase in IL-4, IL-10, and IL-13 levels after TACE. With regard to hepatic events, IL-2 and IL-22 levels at baseline were predictive of grade 3 or more hepatic toxicity, while those levels of IL-6 and IL-13 significantly increased at day 3 in patients suffering from post- TACE hepatic morbidity. Conclusions: TACE induces various changes of multiple cytokines. Distinct panels of cytokine changes are not uniform, influenced by treatment-induced inflammation, underlying liver function, and HCC stage. The increased Th2 cytokine profiles after TACE suggests the immune suppression in patients with large tumor and post-treatment hepatitis.

HCC : PE-056 ; Change of cytokine profile following transarterial chemotherapy in patients with hepatocellular carcinoma

( Min Ju Kim ),( Jeong Won Jang ),( Jung Hyun Kwon ),( Chan Ran You ),( Nam Ik Han ),( Chang Don Lee ),( Hyun Suk Jung ),( Dong Wook Jekar ),( Seung Ok Lee ),( Kyu Won Chung ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

Background: Although alterations in cytokine profile after therapy can affect the outcome and prognosis of cancer patients, there are no comprehensive data on multiple cytokine profiles during transarterial chemotherapy (TACE). Methods: Cytometric bead immunoassay was used to simultaneously measure 13 cytokines (interleukin [IL]-12p70, IFN-γ, IL-17A, IL-2, IL-10, IL-9, IL-22, IL-6, IL-13, IL-4, IL-5, IL-1β, and TNF-α) in the sera of 83 patients with hepatocellular carcinoma (HCC) and 18 healthy controls. Those cytokines were serially monitored at baseline, day 3, day 7, and 2 months after TACE in 63 evaluable patients. Results: Serum levels of IL-17A and IL-5 were higher in HCC patients than healthy controls, whereas IL-22 and IL-1β levels were lower in HCC patients. Although the overall patterns of cytokine changes were diverse at each set date, certain cytokines specifically increased after TACE, with the early-phase increase in IL-6 and IL-22 levels and late-phase increase in IL-4, IL-6, and IL-10 levels. With relatively minor changes of cytokines after TACE, Childs B/C group had higher IL-6 and lower IL-22 levels than Childs A group. Patients with larger tumors (>5 cm) had higher IL-6 levels at baseline and showed a transient but significant early-phase increase in IL-6 levels as well as late-phase increase in IL-4, IL-10, and IL-13 levels after TACE. With regard to hepatic events, IL-2 and IL-22 levels at baseline were predictive of grade 3 or more hepatic toxicity, while those levels of IL-6 and IL-13 significantly increased at day 3 in patients suffering from post- TACE hepatic morbidity. Conclusions: TACE induces various changes of multiple cytokines. Distinct panels of cytokine changes are not uniform, influenced by treatment-induced inflammation, underlying liver function, and HCC stage. The increased Th2 cytokine profiles after TACE suggests the immune suppression in patients with large tumor and post-treatment hepatitis.

PM(10)이 A549 Cells에서 전염증성 Cytokine발현에 미치는 영향

김정호 ( Jung Ho Kim ),전효근 ( Hyo Keun Jeon ),김미경 ( Mi Kyeong Kim ),경선영 ( Sun Yong Kyung ),안창혁 ( Chang Hyeok An ),이상표 ( Sang Pyo Lee ),박정웅 ( Jung Woong Park ),정성환 ( Sung Hwan Jeong ) 대한결핵 및 호흡기학회 2006 Tuberculosis and Respiratory Diseases Vol.60 No.6

연구배경: 미세먼지는 여러 가지 유기물과 무기물의 복합체로 그 구성 성분이 시간과 장소에 따라 다르고 모양과 크기도 일정하지 않으며, 특히 지름 10㎛이하의 미세먼지 (particulate matter 10; PM(10))는 흡입이 가능한 입자의 크기여서 하부기관지 및 폐의 가스-교환부분까지 침착하여 호흡기계에 손상을 일으킬 수 있다. 본 연구에서는 황사에 포함된 PM(10)과 비황사 시기에 포집된 PM(10)이 폐상피세포주에 작용하여 전염증성 사이토카인(proinflammatory cytokine) 및 cytokine messenger RNA(mRNA)의 발현에 어떤 영향이 있는지를 관찰하여 기관지 천식과 만성 폐쇄성 폐질환등 호흡기 질환의 증상 악화기전에 미치는 역할을 규명하고자 하였다. 연구방법: 공기 포집기(HV 500F, sibata model)를 이용하여 황사와 비황사 기간에 하루 6시간씩 실외의 장소에서 대기분진을 membrane filter에 포집한 다음, PM(10)입자를 추출하고 폐암 상피세포주인 A549 cells(한국세포은행주)에 PM(10)을 농도에 맞게(10㎍/㎖, 100㎍/㎖, 500㎍/㎖) 노출시켰다. 각각의 노출된 세포로부터 interleukin(IL)-1α, IL-1β, IL-8, granulocyte macrophage colony stimulating factor(GM-CSF)의 mRNA를 역전사중합효소연쇄반응(reverse transcriptase polymerase chain reaction; RT-PCR) 방법으로 측정하였다. 결과: 황사 및 비황사 기간 중 포집된 PM10을 가했을 시 가하지 않은 대조군에 비하여 IL-1α, IL-1β, IL-8, granulocyte macrophage colony stimulating factor (GM-CSF)의 m`RNA와 cytokine의 발현이 유의하게 높았으며, 황사 기간의 고농도의 PM(10)에 노출된 세포의 IL-1α mRNA는 비황사 기간의 PM(10)에 노출된 세포의 mRNA보다 증가되어 있었다. 결론: PM(10)은 A549 cells에서 전염증성 사이토카인의 발현을 증가시키고 비황사 기간보다 황사 기간 중 대기 중에서 채취한 PM(10)에 노출된 A549 cells에서 일부의 전염증성 사이토카인의 mRNA발현을 더욱 증가시키는 것을 알 수 있었다. 따라서 황사 기간의 PM(10)에 의한 일부의 전염증성 사이토카인의 발현 증가가 만성 호흡기 질환의 증상 악화기전에 연관되어 있을 가능성을 시사하였다. Background: PM(10)(Particulate matter with a diameter < 10㎛), which is characterized by different environmental conditions, is a complex mixture of organic and inorganic compounds. The Asian dust event caused by meteorological phenomena can also produce unique particulate matter in affected areas. This study investigated the cytokine produced by A549 epithelial cells exposed to particles collected during both the Asian dust pfenomenon and ambient air particles in a non-dusty period. Method: Air samples were collected using a high volume air sampler(Sibata Model HV500F) with an air flow at 500ℓ/min for at least 6 hours. The cytokine messenger RNA(mRNA) was measured using a reverse transcriptase polymerase chain reaction(RT-PCR). The A549 cells were exposed to 10 to 500㎍/㎖ of a suspension containing PM(10) for 24 hours. Each was compared with those in the non-exposed control cells. Result: The mRNA levels of interleukin(IL)-1α, IL-Iβ , IL-8, and the granulocyte macrophage colony stimulating factor(GM-CSF) increased after veing exposed to PM(10) in the ambient air particles, compared with those in the non-exposed control cells. The increase in IL-1α and IL-8 were dose dependent at a PM(10) concentration between 100㎍/㎖ and 500㎍/㎖. The mRNA level of IL-8 in the A549 epithelial cells was higher during the in the Asian dust period(500㎍/㎖) than during the non dust period. Conclusion: A549 cells exposed to the PM(10) collected during the Asian dust period produce more proinflammatory cytokine than during non-dusty period. This cytokine enhances the local inflammatory response in the airways and can also contribute to the systemic component of this inflammatory process. (Tuberc Respir Dis 2006; 60: 663-672)

Lipopolysaccharide가 배양 각질형성세포 및 말초혈액 단핵구의 Cytokines 유전자 발현에 미치는 영향

윤기성,전재복,김도원,정상립,김문규 慶北大學校 醫科大學 1995 慶北醫大誌 Vol.36 No.4

목적 : 라포다당류(lipopolysaccharde LPS)는 glycolipids 복합물로 인체내의 여러 면역세포, 특히 혈액내의 단핵구/대식세포에 강력하고 다양한 형태의 자극제로 작용, 각종 사이토카인(cytokine)을, 포함한 여러 매개물질의 분비를 야기하며, 배양세포의 자극제로도 흔히 이용된다. 이에 LPS로 자극된 배양 각질형성 세포및 말초혈액 단핵구가 어떤 사이토카인 유전자를 발현하며 양자간에 그 차이는 어떤가를 알아보고자 한다. 대상 및 방법 : 포피절제술과 말초혈액 채취를 통해 얻어진 배양 각질형성세포 및 단핵구를 역전사 및 중합효소 연쇄반응을 사용하여 사이토카인 유전자 발현을 측정하였다. 결과 : 말초혈액 단핵구에서는 5㎍/㎖의 LPS로 자극한 경우 6 시간 및 24 시간 후 모두에서 대조군인 GAPDH를 포함하여 실험한 IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, TGF-α, TGF-β, GM-CSF 등 11 종류의 모든 사이토카인 유전자 발현을 볼 수 있었고 LPS를 주지 않은 군에서는 6 시간 및 24 시간 후 IL-2와 IL-6을 제외한 9 종류의 사이토카인 유전자 발현을 볼 수 있었으며 그 발현의 정도는 약했다. 각질형성세포에서는 LPS 처치 전 24 시간 동안 BPE를 제거한 각질형성세포 배양액을 사용했을 때 LPS를 주지 않은 경우와 5㎍/㎖의 LPS로 자극한 경우 모두 6 시간 및 24 시간 후 다 같이 어떤 유전자 발현도 볼 수 없었으며, 25㎍/㎖의 LPS로 자극한 경우 6 시간 후에는 유전자 발현이 없었으나 24 시간 후에는 IL-1α, IL-1β, IL-8, IL-10, TGF-α, TGF-β 및 GM-CSF의 유전자 발현을 볼 수 있었고, 이들의 발현 정도는 LPS의 농도가 높을수록 강하게 나타났다. 결론 : LPS가 배양 각질형성세포 및 말초혈액 단핵구의 사이토카인 유전자 발현을 자극하나 양세포간에는 뚜렷한 차이가 있었으며, 각질형성세포에서는 BPE가 cytokine 유전자 발현에 상당한 변수로 작용할 수 있음을 관찰할 수 있었다. Lipopolysaccharde(LPS), a complex glycolipids, is the major component of the outermost membrane of Gram-negative bacteria. There is much interest in LPS because it provides a potent and pleiotrophic stimulus for immune cells, both in vitro and in vivo. It has been often used as the stimulant for several cultured cells, and is known to stimulate the keratinocytes to produce several cytokines. To investigate the effects of LPS on cytokine gene expression of cultured keratinocytes and peripheral blood mononuclear cells (PBMC), we examined the transcripts of cytokine genes using the reverse transcription and polymerase chain reaction (RT-PCR) method with 13 cytokine-specifci primers. The results were as follows : 1. LPS in a concentration of 5 ㎍/㎖ increased the transcription of all the cytokines we examined in PBMC, i.e., interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-α, TGF-β and granulocyte/macrophage-colony stimulating factor (GM-CSF). 2. In keratinocytes cultured in the media without bovine pituitary extract(BPE) for the last 24 hours, LPS in a concentration of 5 ㎍/㎖ did not stimulate any cytokine gene expression. However, LPS in a concentration of 25 ㎍/㎖ stimulated cytokine gene expression of IL-1α, IL-1β, TGF-α, TGF-β and GM-CSF-after 24 hours. 3. In keratinocytes cultured in the media containing BPE, LPS in both concentration of 5 ㎍/㎖ and 25 ㎍/㎖ stimulated cytokine gene expression of IL-1α, IL-1β, IL-8, IL-10, TGF-α, TGF-β and GM-CSF after 6 and 24 hours, respectively.

제대 및 신생아 혈중 cytokine(IL₁β, IL6, TNF) 수치의 변화

강진무,김홍식,박인식,이형종 啓明大學校 醫科大學 1993 계명의대학술지 Vol.12 No.3

분만방법에 따른 제대혈과 양수 그리고 감염 및 stress가 있는 신생아혈중과 세포성분을 배양한 상청액의 cytokine치를 ELISA법으로 측정하여 다음과 같은 성적을 얻었다. 제대혈중 IL₁β치는 질식 유도분만때가 질식 자연 분만, 응급 제왕절개 및 계획 제왕절개때보다 유의하게 높았다(p<0.001). 신생아 혈중 IL₁β치는 감염이 동반된 경우와 stress가 동반된 경우에 높았으며, 감염이 동반되었을 때가 stress보다 더 높게 나타났고, 저체중 출생아에서 높았다. 계획 제왕절개시의 제대혈 IL₁β치는 양수보다 낮았다. 질식자연 분만시 제대혈 세포상청액의 IL₁β 혈장치보다 높았고, 양자간에 유의한 상관관계를 보였다(r=0.92, p<0.05). 감염이 동반된 신생아에서 IL₁β치는 혈장치가 높은 경우 세포 상청액치는 낮고, 혈장치가 낮은 경우 세포 상청액치는 높았다. IL6는 감염이 있는 신생아 혈장과 세포 상청액, 양수 등에서 검출되었다. TNF는 감염이 있는 신생아 세포 상청액 8례중 3례에서 측정되었다 The cytokines, interleukin-1β(IL₁β), interleukin-6(IL6) and tumor necrosis factor(TNF) are important mediators of host response to stress and infection. Impaired immune reaction and febrile responses to the infection in newborn period may result from abnormal cytokine regulation and there were difference in the responses between newborn and adult due to the different cytokine regulation system. To investigate the cytokine regulation in different circumstances of the delivery and newborn conditions, the measurement of the levels of IL₁β,IL6 and TNF in cord blood, amniotic fluid and the blood of the newborn were performed, using enzyme linked immunosorbent assay(ELISA,R&D Co.). Cytokines of the supernatant of incubated cellular pellet were also measured. Cord blood IL₁β level was significantly higher in induced vaginal delivery than that of the normal vaginal, emergency, and elective cesarian section delivery(p<0.001). Plasma IL₁β level of the newborn with infection or stress was elevated and the level was higher in infection than that of the newborn with stress during delivery. Premature baby had higher level than normal newborn. Cord blood IL₁βlevel was lower than that of amniotic fluid in elective cesarian section delivery. In normal vaginal delivery, IL₁βlevel of the cellular supernatant was higher than that of the plasma and showed good correlation(r=0.92, p<0.05). In newborn with infection, plasma IL₁βlevel was high in the cases with low supernatant level and the plasma level was low in the cases with high supernatant IL₁β. IL6 was detcted from the plasma and cellular supernatant of the newborn with infection and the amniotic fluid. TNF was detected in cellular supernatant of 3 among 8 newborn with infection.

Cytokine의 세포 내 신호전달 과정의 억제 기전 (Jak-STAT Signaling을 중심으로)

지종대 ( Jong Dae Ji ),이영호 ( Young Ho Lee ),송관규 ( Gwan Gyu Song ) 대한류마티스학회 2003 대한류마티스학회지 Vol.10 No.1

Cytokines are secreted proteins and interact with their specific cell surface receptors, triggering intracellular signal transduction pathways that activate a number of genes crucial for the biological functions of cytokines. These cytokine signal transduction pathways are tightly regulated processes. The negative regulations of cytokine signaling are achieved by receptor internalization and degradation, dephosphorylation of signaling intermediates, expression of protein inhibitors such as suppressor of cytokine signaling (SOCS) and protein inhibitors of activated STAT (PIAS). The observation that cytokines are central to the inflammatory and destructive process in several autoimmune diseases suggests that interventions targeting the cytokine intracellular signaling will be a new therapeutic strategy in autoimmune diseases. We review the current knowledge about negative regulation of cytokine signal transduction.

역전사 중합효소연쇄반응을 이용한 태아혈액의 Interleukin-1β, Tumor Necrosis Factor-α, Transforming Growth Factor-β의 발현양상

최석태 ( Seok Tae Choi ),윤보현 ( Bo Hyun Yoon ),신희철 ( Hee Chul Syn ) 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.12

Background: For the successful pregnancy, the feto-maternal immunologic bidirectional interaction should be programed to accept the fetal semiallograft and assist the feto-placental growth in early pregnancy. It has been known that these signaling materials for interacting are cytokines. Up to the present, the potential roles of cytokines in normal pregnancy are, first, as a signal material of maternal immunologic recognition of fetal semiallograft, second, as a substance like growth- factor to promote the feto-placental growth and differentiation, third, as a material to alter the maternal immunity for fetal survival, fourth, as a mediator to initiate or prevent the labor. We have proposed the hypothesis that various cytokines may be expressed simultaneously, and then, may regulate the maintenance of pregnancy by interacting with each other harmonically after midpregnancy. Because the maintenance of pregnancy and the mechanism of labor depend on the total effect of various cytokines rather than the effect of one specific cytokine. Objectives: To support a potential role of the fetus itself for participating in the bidirectional cytokine regulatory network, and support our hypothesis that various cytokines may be expressed simultaneously, and then, may regulate the maintenance of pregnancy by interacting with each other harmonically after midpregnancy. Study dasign: For exploring the actual immunologic status of fetus itself in utero, we have chosen the seventeen fetal blood samples which have been taken at the cordocentesis or at the delivery without labor after midpregnancy(20th~39th weeks of gestation). After extracting the RNA from these fetal blood samples, we have tried to demonstrate the expression of interleukin-1β and tumor necrosis factor-a mRNA, and simultaneously, demonstrate the expression of transforming growth factor-β mRNA by using reverse transcriptase-po1ymerase chain reaction(rt-PCR) technique. Results: In this study we found that the expression of interleukin-1β mRNA was demonstrated from as early as 22nd weeks to term gestation, and the expression of tumor necrosis factor-α mRNA was demonstrated from as early as 2300rd weeks to term gestation, and the expression of transforming growth factor-β mRNA was demonstrated from as early as 21st weeks to term gestation. Conclusion: On the basis of these findings, first, we support the result of recent study that the fetus itself may participate in the bidirectional cytokine regulatory network after midpregnancy, second, we prove the possible hypothsis that various cytokines may be expressed simultaneously, and then, may regulate the maintenance of pregnancy by interacting with each other harmonically after mid pregnancy.