Nod-like receptors in infectious diseases Jong-Hwan Park Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University Nod-like receptors (NLRs) are intracellular, cytoplasmic sensor for microbial components and danger signals. There are 23 NLR family members in humans and at least 34 genes in mice. NLRs are expressed in nonimmune cells including epithelial cells and mesothelial cells as well as immune cells. As first identified NLRs, Nod1 and Nod2 consist of N-terminal caspase recruitment domain (CARD), intermediate nucleotide-binding oligomerization domain (NOD), and C-terminal leucine-rich repeats (LRRs) domain. Nod1 and Nod2 recognize peptidoglycan derivatives, meso-diaminopimelic acid (meso-DAP) and muramyl dipeptide (MDP), respectively. After stimulated by their specific bacterial molecules, Nod1 and Nod2 associate with its adaptor molecule, RICK/Rip2/CARDIAK, through CARD-CARD interaction, which leads to activation of NF-κB and MAPK, followed by induction of numerous genes involved in inflammatory process. In addition, several types of NLRs including NLRC4 and NLRP3 contribute to the activation of inflammasome, resulting in caspase-1 cleavage. This process is essential for maturation of IL-1β and IL-18. We discuss here the role of NLR proteins in inflammatory diseases. CURRICULUM VITAE Name: Park, Jong-Hwan, Ph.D and DVM Sex: Male Date of Birth: Feb/05/1976 ID number: 760205-******* 1. Business Address: Department of Laboratory Animal Medicine Tel: +82-62-530-2834 College of Veterinary Medicine, Chonnam National University Fax: +82-42-600-6450 77 Yong-Bong ro, Buk-gu C.P: +82-10-4379-6967 Gwangju 500-757, South Korea E-mail: [email protected] 2. Home Address: 1209-dong 103-ho, Neuriul 12 complex Tel: +82-70-8200-6967 184 Gwanjeo Rd, Seo-gu Daejeon, 302-785 South Korea 3. Education Year Conferring Institution Field Degree 2005. 2. Seoul National University Laboratory Animal Medicine Ph.D 2000. 2. Seoul National University Laboratory Animal Medicine MS 1998. 2. Seoul National University Veterinary Medicine DVM 4. Titles of Thesis Year Titles Degree 2000. 2. Experimental infection of mice with homogenate from a porcine MS stomach infected with tightly spiral bacteria 2005. 2. Pathological characteristics of gastritis induced by Listeria Ph.D monocytogenes infection via intragastric route in mice 5. Employments Duration Institutes Title 2003. 9. - 2005. 4. Laboratory Animal Center, Research Assistant Seoul National University 2005. 5. – 2009. 1. Department of Pathology, Research Fellow University of Michigan (postdoctoral) 2009. 2. – 2010. 2. School of Dentistry, Research Professor Chosun University 2009. 12. – present WCI program Participating KRIBB Researcher 2010. 3. – 2012. 3. Department of Biochemistry Full-time Konyang University Instructor 2012. 04. – 2014. 08 Department of Biochemistry Assistant professor Konyang University 2014. 09 - present Department of Laboratory Animal Medicine, College of Veterinary Assistant professor Medicine, Chonnam National University 6. Awards Date Issuing Institutes Name of Prize College of Veterinary Medicine Baek-lin Research 2004. 11. 5 Seoul National University Encouragement Prize Japanese Association for Laboratory 2010. 05. 13 International Award Animal Science 7. Research projects 연구비 기간 지원기관 연구주제 자격 (천원) 한국연구재단 Helicobacter pylori 감염에 의한 위염 및 위암에 2009. 5. 1 - 책임 (일반연구자지원 관여하는 숙주 면역반응에서Toll-like receptor와 155,820 2012. 4. 30 연구원 사업 – 기본연구) Nod-like receptor signaling의 역할 한국보건산업진흥원 2009. 5. 1 – 구강암의 진행에 미치는 구강 미생물의 영향과 책임 (보건의료연구개발 35,000 2010. 4. 30 Toll-like receptor 및 Nod-like receptor의 역할 연구원 사업) 2009. 12. 1 – 한국연구재단 세부 WCI kinomics 기반 항암연구센터 270,000 2014. 11. 30 (WCI 사업) 책임 한국연구재단 2010. 5. 1 - 전립선의 염증 및 발암 과정을 조절하는 선천면역 책임 (일반연구자지원 144,900 2013. 4. 30 기전 연구: TLR/NLR 신호기전 연구 연구원 사업-신진연구) 2010. 8. 1 – 국방과학연구소 흑사병계열 세균감염에 대항하는 숙주면역 유발 책임 96,500 2012. 12. 31 (순수기초연구사업) 기전에 관한 연구 연구원 2011. 5. 1 – 한국보건산업진흥원 수지상세포 기반 알러지성 천식요법 개발 900,000 세부 2014. 3. 31 (중점연구) (175,000) 책임 한국연구재단 2012. 9. 1 – 다재내성균 Acinetobacter baumannii에 의한 책임 (일반연구자지원 162,150 2015. 8. 31 항생 펩타이드 생성기전 연구 연구원 사업-기본연구) 2012. 9. 1 – 국방과학연구소 Yersinia에 대한 생체 내 방어인자 생성기전 및 책임 395,000 2015. 8. 31 (국제공동연구사업) 효과연구 연구원 한국보건산업진흥원 2013. 7. 1 – 고병원성 한국형 결핵균 K 균주의 핵심 병원성 인자에 900,000 세부 (난치성 결핵 2015. 6. 30 의한 병인면역과 방어면역의 프로그램화 기전 규명 (270,000) 책임 극복기술개발 사업) * Gray: finished 8. Oral presentation 2010. 05. 12 – 2010. 05. 14: Kyoto Terrsa (Kyoto, Japan) Jong-Hwan Park, Seung-Hyeok Seok, Min-Won Baek, Hui-Young Lee, Dong-Jae Kim, and Jae-Hak Park. Gastric lesions and immune responses caused by long-term infection with Helicobacter heilmannii in C57BL/6 mice. The 57th Annual Meeting of the Japanese Association for Laboratory Animal Science. 2011. 05. 13 – 2011. 05. 14: Grand Hilton Hotel (Seoul, Korea) Jong-Hwan Park. Toll-like receptors and Nod-like receptors in Infection. 2011 The 19th Federation Meeting of Korean Basic Medical Scientists. 2011. 06. 22 – 2011. 06. 24: Hotel Hyundai (Gyeongju, Korea) Jong-Hwan Park. Toll-like receptors and Nod-like receptors in Infection. 2011 International Symposium & Annual Meeting: Translational Research in Microbiology and Biotechnology. 2012. 08. 23 – 2012. 08. 25: Lotte Buyeo Resort (Chungcheongnam-do, Korea) Jong-Hwan Park: TLR signaling in Acinetobacter baumannii infection. 2012 KALAS International Symposium 9. Poster presentation 2010. 08. 19 – 2010. 08. 21: Bexco (Busan, Korea) Min-Jung Kang, Eun-Jung Song, Kyung-Bok Lee, Sang-Muk Oh, and Jong-Hwan Park. TLR2 activation promotes the expression of VEGF in human prostate cancer. 25th KALAS International Symposium. 2011. 02. 12 – 2011. 02. 17: Santa Fe Community Convention Center Eun-Jung Song, Min-Jung Kang, and Jong-Hwan Park. Toll-like receptor 5 mediates the proliferation of gastric cancer cells via ERK-dependent pathway. 40th Keystone Symposia: Cancer Control by Tumor Suppressors and Immune Effectors. Publications I. International Journals (SCI & SCIE) I-86. Tae-Hyoun Kim, Sung Jae Shin, Yeong-Min Park, In Duk Jung, Seung-Wook Ryu, Dong-Jae Kim, Jae-Hak Park, Jong-Hwan Park (2015) Critical role of TRIF and MyD88 in Hsp70-mediated activation of dendritic cells. Cytokine, 71(2):139-144. I-85. Min-Jung Kang, Eun-Jung Song, Bo-Yeon Kim, Dong-Jae Kim and Jong-Hwan Park (2014) Helicobacter pylori induces vascular endothelial growth factor production in gastric epithelial cells through hypoxia-inducible factor-1α-dependent pathway. Helicobacter, 19(6):476-483. I-84. Yu-Jin Jeong, Min-Jung Kang, Sang-Jin Lee, Chang-Hwan Kim, Jee-Cheon Kim, Tae-Hyoun Kim, Dong-Jae Kim, Donghyun Kim, Gabriel Núñez, and Jong-Hwan Park (2014) Nod2 and Rip2 contribute to innate immune responses in mouse neutrophils. Immunology, 143(2):269-276. I-83. Jong-Jin Kim, Yun-Ho Hwang, Kyung-Yun Kang, Inbo Kim, Jong-Bae Kim, Jong-Hwan Park, Yung-Choon Yoo, and Sung-Tae Yee (2014) Enhanced dendritic cell maturation by the B-chain of Korean mistletoe lectin (KML-B), a novel TLR4 agonist. International Immunopharmacology, 21(2):309-319. I-82. Se-Ra Park, Dong-Jae Kim, Seung-Hyun Han, Min-Jung Kang, Jun-Young Lee, Yu-Jin Jeong, Sang-Jin Lee, Tae-Hyoun Kim, Sang-Gun Ahn, Jung-Hoon Yoon, and Jong-Hwan Park (2014) Diverse toll-like receptors mediate cytokines production by Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans in macrophages. Infection and Immunity, 82(5):1914-1920. I-81. Tae-Hyoun Kim, Yeong-Min Park, Seung-Wook Ryu, Dong-Jae Kim, Jae-Hak Park, and Jong-Hwan Park (2014) Receptor interacting protein 2 (Rip2) is dispensable for OVA-induced airway inflammation in mice. Allergy, Asthma & Immunology Research, 6(2):163-168. I-80. Chang-Hwan Kim, Dong-Jae Kim, Sang-Jin Lee, Yu-Jin Jeong, Min-Jung Kang, Jun-Young Lee, Jin-A Choi, Sun-Jung Kwon, Jae-Hak Park and Jong-Hwan Park (2014) Toll-like receptor 2 promotes bacterial clearance during the initial stage of pulmonary infection with Acinetobacter baumannii. Molecular Medicine Reports, 9(4):1410-1414. I-79. Jung-Hwan Park, Yu-Jin Jeong, Hee Kwan Won, Sang-Yun Choi, Jong-Hwan Park, Sang-Muk Oh (2014) Activation of TOPK by lipopolysaccharide promotes induction of inducible nitric oxide synthase through NF-κB activity in leukemia cells. Cellular Signalling, 26(5):849-856. I-78. Ki Bum Ahn, Jun Ho Jeon, Jung Eun Baik, Ok-Jin Park, Seok-Seong Kang, Cheol-Heui Yun, Jong-Hwan Park, and Seung Hyun Han (2014) Muramyl dipeptide potentiates staphylococcal lipoteichoic acid induction of cyclooxygenase-2 expression in macrophages. Microbes and Infection, 16(2):153-160. I-77. , , , , , , , , , , , Jong-Hwan Park* (Co-corresponding author), * (2013) Human Umbilical Cord Blood Mesenchymal Stem Cells Reduce Colitis in Mice by Activating NOD2 Signaling to COX2. Gastroenterology, 145(6):1392-1403. I-76. Yu-Jin Jeong, Chang-Hwan Kim, Jee-Cheon Kim, Sang-Muk Oh, Kyung-Bok Lee, Jong-Hwan Park* (Co-corresponding author), and Dong-Jae Kim* (2013) RIP2/RICK-dependent cytokine production upon Yersinia enterocolitica infection in macrophages with TLR4-deficiency. Scandinavian Journal of Immunology, 78(5):401-407. I-75. Dong-Jae Kim*, Jong-Hwan Park* (co-first author), Luigi Franchi, Steffen Backert and Gabriel Núñez (2013) The Cag pathogenicity island and interaction between TLR2/NOD2 and NLRP3 regulate IL-1β production in Helicobacter pylori infected dendritic cells. European Journal of Immunology, 43(10):2650-2658. I-74. Jong-Seok Kim, Woo Sik Kim, Han-Gyu Choi, Byungki Jang, Keehoon Lee, Jong-Hwan Park, Hwa-Jung Kim, Sang-Nae Cho, and Sung Jae Shin (2013) Mycobacterium tuberculosis RpfB drives Th1-type T cell immunity via a TLR4-dependent activation of dendritic cells. Journal of Leukocyte Biology, 94(4):733-749. I-73 MY Ahn, H-E Yoon, J-H Park, J Lee, S-K Min, S-G Ahn, J-H Yoon (2013) Characterization of NODs and TLRs in innate immune response of human cementoblast cells.