Brown Adipocyte and Splenocyte Co-Culture Maintains Regulatory T Cell Subset in Intermittent Hypobaric Conditions

강태흥,Jung Hwa Park,Donghyeok Shin,Hyungon Choi,Jeenam Kim,이명철 한국조직공학과 재생의학회 2019 조직공학과 재생의학 Vol.16 No.6

BACKGROUND: Brown adipocytes have thermogenic characteristics in neonates and elicit anti-inflammatory responses. We postulated that thermogenic brown adipocytes produce distinctive intercellular effects in a hypobaric state. The purpose of this study is to analyze the correlation between brown adipocyte and regulatory T cell (Treg) expression under intermittent hypobaric conditions. METHODS: Brown and white adipocytes were harvested from the interscapular and flank areas of C57BL6 mice, respectively. Adipocytes were cultured with syngeneic splenocytes after isolation and differentiation. Intermittent hypobaric conditions were generated using cyclic negative pressure application for 48 h in both groups of adipocytes. Expression levels of Tregs (CD4 ? CD25 ? Foxp3 ? T cells), cytokines [tumor necrosis factor-a (TNF-a) and interleukin- 10 (IL-10), and the programmed death-ligand 1 (PD-L1)] co-inhibitory ligand were examined. RESULTS: Splenocytes, cultured with brown and white adipocytes, exhibited comparable Treg expression in a normobaric state. Under hypobaric conditions, brown adipocytes maintained a subset of Tregs. However, a decrease in Tregs was found in the white adipocyte group. TNF-a levels increased in both groups under hypobaric conditions. In the brown adipocyte group, anti-inflammatory IL-10 expression increased significantly; meanwhile, IL-10 expression decreased in the white adipocyte group. PD-L1 levels increased more significantly in brown adipocytes than in white adipocytes under hypobaric conditions. CONCLUSION: Both brown and white adipocytes support Treg expression when they are cultured with splenocytes. Of note, brown adipocytes maintained Treg expression in intermittent hypobaric conditions. Anti-inflammatory cytokines and co-inhibitory ligands mediate the immunomodulatory effects of brown adipocytes under altered atmospheric conditions. Brown adipocytes showed the feasibility as a source of adjustment in physical stresses.

산야초의 사료적 가치와 이용

강태흥 한국낙농육우협회 1985 낙농·육우 Vol.43 No.-

오디오 변환부호화기에서 인간 청각 음압 감도 특성에 근거한 비트 할당 기법 ( A Method of Bit Allocation Based on Sound Pressure Level of Audibility in Audio Transform Coder )

강태흥,김경규,장충환,이건일 대한전자공학회 1995 대한전자공학회 학술대회 Vol.1995 No.1

총설 : RNAi 기술을 이용한 항암면역 치료

김태우,김진희,강태흥 한국생화학분자생물학회 (구 한국생화학회) 2008 생화학분자생물학회 소식 Vol.28 No.1

Induction of Immunity Against Hepatitis B Virus Surface Antigen by Intranasal DNA Vaccination Using a Cationic Emulsion as a Mucosal Gene Carrier

김태우,정서영,정혜선,권익찬,성하진,강태흥,Hee Dong Han 한국분자세포생물학회 2006 Molecules and cells Vol.22 No.2

자궁경부암 동물 모델에서 PEG/PLLA copolymer sysetm을 사용한 Paclitaxel 국소 투여의 효과

김찬주,이용석,이근호,정병문,김태우,강태흥,김희숙,박종섭 대한부인종양학회 2008 Journal of Gynecologic Oncology Vol.19 No.1

Objective : Paclitaxel is one of the most effective antineoplastic drugs. HPV-related cervical lesions have only managed with invasive procedure or observation. After the introduction of PHV prophylactic vaccine, there are no remarkable improvements. This ineffectiveness can in part be attributed to inadequate durg and delivery methods. Topical drug administration with temperature sensitive copolymer gels are useful approaches to clinical situation. In this study, we evaluated the activity of multiblock copolymers of PEG/PLA (poly(L-lactic acid)/polyethylene glycol) gels with paclitaxel (PTX) formulation administered by topical treatment to mice bearing human cervical cancer cell lines (HeLa). Methods : We have synthesized gels of PEG/PLLA (poly(L-lactic acid)/polyethylene glycol) multiblock copolymers containing Paclitaxel which have temperature-sensitivecharacteristics. This Paclitaxel- containg copolymers has the sol-gel-sol transition temperature at body temperature. The efficacy of PTX in PEG/PLA mutiblock copolymer micelle were conducted in HeLa-tumor bearing Balb/c Nu/Nu athymic mice at an equivalent paclitaxel dose of 10 mg/kg with 48 hr interval. The inhibition of tumor growth was evaluated after 8days of treatment. Tumors were harvested at day 10 and stained with hematoxylin and eosine to measure tumor. RESULTS: PTX-containing PEG/PLA mutiblock copolymer significantly decreased tumor growth at day 8, as measured by tumor size; ie, PEG/PLA mutiblock copolymer only goup ; 1.43+0.26m versus intraperitoneal treatment of Paclitaxel : 0.75+0.07mm and topical treatment of PTX-containing PEG/PLA copolymer containing Paclitaxel : 0.28mm (Min; 0.1mm-Max:0.8mm) CONCLUSION: This demonstration that PTX-containing PEG/PLA mutiblock copolymer have a useful topical drug deliversy system carrying temperature sensitive characetersitics in HPV-related cervical lesions. 목적 : Paclitaxel은 최근 널리사용되는 가장 효과적인 항암제이다. HPV관련성 자궁 경부 질환은 최근 개발된 HPV예방백신이 있지만, 침습적인 수술방법이나 관찰외에는 뚜렷한 치료법이 없다. 그 이유는 현재까지 개발된 효과적인 치료 약물과 부작용이 적은 약물 투여법이 없기 때문이다. 이에 온도 민감성 copolymer 젤을 국소적으 로 투여하는 방법이 효과적인 임상 적용에 유리하다. 이에 Paclitaxel(PTX)을 함유하고 체온 범위에서 젤이 되 는 온도 민감성 PEG/PLA (poly(L-lactic acid)/polyethylene glycol) 을 HPV양성인 자궁 경부암 세포주(HELa) 의 성장 억제에 효과가 있는지 알아보았다. 방법: Paclitaxel을 함유한 PEG/PLLA (poly(L-lactic acid)/polyethylene glycol) multiblock copolymer중 체 온 범위에서 젤이 되도록 만들어 사용하였다. Paclitaxel-PEG/PLLA 젤의 효과는 Balb/c Nu/Nu athymic mice에 대하여 주입된 HeLa 세포주의 크기 변화를 측정하였다. 48시간 간격으로 2회 Paclitaxel (10mg/kg)을 투여 한 뒤8일째까지 종양 크기를 측정하고, 마지막날 종양을 적출하여 헤마톡실린-에오신 염색으로 크기를 확인하였 다. 결과:Paclitaxel- PEG/PLA 다원 공중합체를 투여한 지 8일째에, 쥐에서 xenograft tumors (HeLa cells; HPV-18 positive state)의 종양성장 억제가 관찰이 되었다. PEG/PLA 다원 공중합체만 투여한 경우에는 종양의 크기가 1.43+0.26mm 이였으며, Paclitaxel을 복강내 주사한 경우에는 0.75+0.07mm 였다. Paclitaxel-PEG/PLA copolymer 를 경피적으로투여한 경우에 0.28m (최소 0.1mm-최대 0.8mm)였다. 결론 : HPV-관련성 자궁 경부 질환의 치료에 Paclitaxel을 함유한 PEG/PLA mutiblock copolymer는 체온 범위에 서 젤이 되는 성질을 가진 유용한 약물치료법이 될 것이다.

Interactions between tumor-derived proteins and Toll-like receptors

Jang Gun-Young,이지원,김영섭,이성은,Hee Dong Han,Hong Kee-Jong,강태흥,박영민 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Damage-associated molecular patterns (DAMPs) are danger signals (or alarmins) alerting immune cells through pattern recognition receptors (PRRs) to begin defense activity. Moreover, DAMPs are host biomolecules that can initiate a noninflammatory response to infection, and pathogen-associated molecular pattern (PAMPs) perpetuate the inflammatory response to infection. Many DAMPs are proteins that have defined intracellular functions and are released from dying cells after tissue injury or chemo-/radiotherapy. In the tumor microenvironment, DAMPs can be ligands for Toll-like receptors (TLRs) expressed on immune cells and induce cytokine production and T-cell activation. Moreover, DAMPs released from tumor cells can directly activate tumor-expressed TLRs that induce chemoresistance, migration, invasion, and metastasis. Furthermore, DAMP-induced chronic inflammation in the tumor microenvironment causes an increase in immunosuppressive populations, such as M2 macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). Therefore, regulation of DAMP proteins can reduce excessive inflammation to create an immunogenic tumor microenvironment. Here, we review tumor-derived DAMP proteins as ligands of TLRs and discuss their association with immune cells, tumors, and the composition of the tumor microenvironment.

Nanoparticle-Based Vaccine Delivery for Cancer Immunotherapy

박영민,이승준,Young Seob Kim,Moon Hee Lee,Gil Sun Cha,정인덕,강태흥,한희동 대한면역학회 2013 Immune Network Vol.13 No.5

Development of nano-sized carriers including nanoparticles, nanoemulsions or liposomes holds great potential for advanced delivery systems for cancer immunotherapy, as such nanostructures can be used to more effectively manipulate or deliver immunologically active components to specific target sites. Successful development of nanotechnology based platform in the field of immunotherapy will allow the application of vaccines, adjuvants and immunomodulatory drugs that improve clinical outcomes for immunological diseases. Here, we review current nanoparticle-based platforms in the efficacious delivery of vaccines in cancer immunotherapy

Cordyceps sp. MET 1504 가 생산하는 Exo-β-D-Glucosaminidase 의 분리정제 및 특성에 관한 연구

신선오(Sun Oh Shin),정기철(Ki Chul Chung),강태흥(Tae Hung Kang) 한국키틴키토산학회 2001 한국키틴키토산학회지 Vol.6 No.4

N/A N/A

CTHRC1 promotes angiogenesis by recruiting Tie2-expressing monocytes to pancreatic tumors

이재민,송진회,권은수,Seongyea Jo,강민경,김연정,황연실,배호성,강태흥,장수환,조희준,김송철,김석호,고상석 생화학분자생물학회 2016 Experimental and molecular medicine Vol.48 No.-

CTHRC1 (collagen triple-helix repeat-containing 1), a protein secreted during the tissue-repair process, is highly expressed in several malignant tumors, including pancreatic cancer. We recently showed that CTHRC1 has an important role in the progression and metastasis of pancreatic cancer. Although CTHRC1 secretion affects tumor cells, how it promotes tumorigenesis in the context of the microenvironment is largely unknown. Here we identified a novel role of CTHRC1 as a potent endothelial activator that promotes angiogenesis by recruiting bone marrow-derived cells to the tumor microenvironment during tumorigenesis. Recombinant CTHRC1 (rCTHRC1) enhanced endothelial cell (EC) proliferation, migration and capillary-like tube formation, which was consistent with the observed increases in neovascularization in vivo. Moreover, rCTHRC1 upregulated angiopoietin-2 (Ang-2), a Tie2 receptor ligand, through ERK-dependent activation of AP-1 in ECs, resulting in recruitment of Tie2-expressing monocytes (TEMs) to CTHRC1-overexpressing tumor tissues. Treatment with a CTHRC1-neutralizing antibody-abrogated Ang-2 expression in the ECs in vitro. Moreover, administration of a CTHRC1-neutralizing antibody to a xenograft mouse model reduced the tumor burden and infiltration of TEMs in the tumor tissues, indicating that blocking the CTHRC1/Ang-2/TEM axis during angiogenesis inhibits tumorigenesis. Collectively, our findings support the hypothesis thatCTHRC1 induction of the Ang-2/Tie2 axis mediates the recruitment of TEMs, which are important for tumorigenesis and can be targeted to achieve effective antitumor responses in pancreatic cancers. CTHRC1 (collagen triple-helix repeat-containing 1), a protein secreted during the tissue-repair process, is highly expressed in several malignant tumors, including pancreatic cancer. We recently showed that CTHRC1 has an important role in the progression and metastasis of pancreatic cancer. Although CTHRC1 secretion affects tumor cells, how it promotes tumorigenesis in the context of the microenvironment is largely unknown. Here we identified a novel role of CTHRC1 as a potent endothelial activator that promotes angiogenesis by recruiting bone marrow-derived cells to the tumor microenvironment during tumorigenesis. Recombinant CTHRC1 (rCTHRC1) enhanced endothelial cell (EC) proliferation, migration and capillary-like tube formation, which was consistent with the observed increases in neovascularization in vivo. Moreover, rCTHRC1 upregulated angiopoietin-2 (Ang-2), a Tie2 receptor ligand, through ERK-dependent activation of AP-1 in ECs, resulting in recruitment of Tie2-expressing monocytes (TEMs) to CTHRC1-overexpressing tumor tissues. Treatment with a CTHRC1-neutralizing antibody-abrogated Ang-2 expression in the ECs in vitro. Moreover, administration of a CTHRC1-neutralizing antibody to a xenograft mouse model reduced the tumor burden and infiltration of TEMs in the tumor tissues, indicating that blocking the CTHRC1/Ang-2/TEM axis during angiogenesis inhibits tumorigenesis. Collectively, our findings support the hypothesis that CTHRC1 induction of the Ang-2/Tie2 axis mediates the recruitment of TEMs, which are important for tumorigenesis and can be targeted to achieve effective antitumor responses in pancreatic cancers.