NAMPT mitigates colitis severity by supporting redox-sensitive activation of phagocytosis in inflammatory macrophages
Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD+) salvage pathway and plays a crucial role in the maintenance of the NAD+ pool during inflammation. Considering that macrophages are essential for tissue homeostasis and inflammat...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221323172200009X |
| _version_ | 1818331980599656448 |
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| author | Sun Mi Hong A-Yeon Lee Sung-Min Hwang Yu-Jin Ha Moo-Jin Kim Seongki Min Won Hwang Gyesoon Yoon So Mee Kwon Hyun Goo Woo Hee-Hoon Kim Won-Il Jeong Han-Ming Shen Sin-Hyeog Im Dakeun Lee You-Sun Kim |
| author_facet | Sun Mi Hong A-Yeon Lee Sung-Min Hwang Yu-Jin Ha Moo-Jin Kim Seongki Min Won Hwang Gyesoon Yoon So Mee Kwon Hyun Goo Woo Hee-Hoon Kim Won-Il Jeong Han-Ming Shen Sin-Hyeog Im Dakeun Lee You-Sun Kim |
| author_sort | Sun Mi Hong |
| collection | DOAJ |
| description | Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD+) salvage pathway and plays a crucial role in the maintenance of the NAD+ pool during inflammation. Considering that macrophages are essential for tissue homeostasis and inflammation, we sought to examine the functional impact of NAMPT in inflammatory macrophages, particularly in the context of inflammatory bowel disease (IBD). In this study, we show that mice with NAMPT deletion within the myeloid compartment (Namptf/fLysMCre+/-, Nampt mKO) have more pronounced colitis with lower survival rates, as well as numerous uncleared apoptotic corpses within the mucosal layer. Nampt-deficient macrophages exhibit reduced phagocytic activity due to insufficient NAD+ abundance, which is required to produce NADPH for the oxidative burst. Nicotinamide mononucleotide (NMN) treatment rescues NADPH levels in Nampt mKO macrophages and sustains superoxide generation via NADPH oxidase. Consequently, Nampt mKO mice fail to clear dead cells during tissue repair, leading to substantially prolonged chronic colitis. Moreover, systemic administration of NMN, to supply NAD+, effectively suppresses the disease severity of DSS-induced colitis. Collectively, our findings suggest that activation of the NAMPT-dependent NAD+ biosynthetic pathway, via NMN administration, is a potential therapeutic strategy for managing inflammatory diseases. |
| first_indexed | 2024-12-13T13:28:28Z |
| format | Article |
| id | doaj.art-4f84bec6185c4c0ca0541ee759f35cbb |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-13T13:28:28Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-4f84bec6185c4c0ca0541ee759f35cbb2022-12-21T23:44:14ZengElsevierRedox Biology2213-23172022-04-0150102237NAMPT mitigates colitis severity by supporting redox-sensitive activation of phagocytosis in inflammatory macrophagesSun Mi Hong0A-Yeon Lee1Sung-Min Hwang2Yu-Jin Ha3Moo-Jin Kim4Seongki Min5Won Hwang6Gyesoon Yoon7So Mee Kwon8Hyun Goo Woo9Hee-Hoon Kim10Won-Il Jeong11Han-Ming Shen12Sin-Hyeog Im13Dakeun Lee14You-Sun Kim15Department of Biochemistry, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of KoreaDepartment of Biochemistry, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea; Department of Biomedical Sciences, Graduate School of Ajou University, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of KoreaDepartment of Biochemistry, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of KoreaDepartment of Biochemistry, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea; Department of Biomedical Sciences, Graduate School of Ajou University, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of KoreaDepartment of Biochemistry, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea; Department of Biomedical Sciences, Graduate School of Ajou University, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of KoreaDepartment of Biochemistry, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea; Department of Biomedical Sciences, Graduate School of Ajou University, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of KoreaMSBIOTECH. LTD, Chungbuk, 27672, Republic of KoreaDepartment of Biochemistry, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea; Department of Biomedical Sciences, Graduate School of Ajou University, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of KoreaDepartment of Physiology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of KoreaDepartment of Biomedical Sciences, Graduate School of Ajou University, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea; Department of Physiology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of KoreaLaboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaLaboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaFaculty of Health Sciences, University of Macau, Macau, ChinaDepartment of Life Sciences, Pohang University of Science and Technology, Pohang, 37673, Republic of Korea; ImmunoBiome, Bio Open Innovation Center, Pohang, 37673, Republic of KoreaDepartment of Pathology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea; Corresponding author. Department of Pathology, Ajou University School of Medicine164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea.Department of Biochemistry, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea; Department of Biomedical Sciences, Graduate School of Ajou University, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea; Corresponding author. Department of Biochemistry, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea.Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD+) salvage pathway and plays a crucial role in the maintenance of the NAD+ pool during inflammation. Considering that macrophages are essential for tissue homeostasis and inflammation, we sought to examine the functional impact of NAMPT in inflammatory macrophages, particularly in the context of inflammatory bowel disease (IBD). In this study, we show that mice with NAMPT deletion within the myeloid compartment (Namptf/fLysMCre+/-, Nampt mKO) have more pronounced colitis with lower survival rates, as well as numerous uncleared apoptotic corpses within the mucosal layer. Nampt-deficient macrophages exhibit reduced phagocytic activity due to insufficient NAD+ abundance, which is required to produce NADPH for the oxidative burst. Nicotinamide mononucleotide (NMN) treatment rescues NADPH levels in Nampt mKO macrophages and sustains superoxide generation via NADPH oxidase. Consequently, Nampt mKO mice fail to clear dead cells during tissue repair, leading to substantially prolonged chronic colitis. Moreover, systemic administration of NMN, to supply NAD+, effectively suppresses the disease severity of DSS-induced colitis. Collectively, our findings suggest that activation of the NAMPT-dependent NAD+ biosynthetic pathway, via NMN administration, is a potential therapeutic strategy for managing inflammatory diseases.http://www.sciencedirect.com/science/article/pii/S221323172200009XNAMPTColitisMacrophagePhagocytic activityNAD+Inflammatory bowel disease |
| spellingShingle | Sun Mi Hong A-Yeon Lee Sung-Min Hwang Yu-Jin Ha Moo-Jin Kim Seongki Min Won Hwang Gyesoon Yoon So Mee Kwon Hyun Goo Woo Hee-Hoon Kim Won-Il Jeong Han-Ming Shen Sin-Hyeog Im Dakeun Lee You-Sun Kim NAMPT mitigates colitis severity by supporting redox-sensitive activation of phagocytosis in inflammatory macrophages Redox Biology NAMPT Colitis Macrophage Phagocytic activity NAD+ Inflammatory bowel disease |
| title | NAMPT mitigates colitis severity by supporting redox-sensitive activation of phagocytosis in inflammatory macrophages |
| title_full | NAMPT mitigates colitis severity by supporting redox-sensitive activation of phagocytosis in inflammatory macrophages |
| title_fullStr | NAMPT mitigates colitis severity by supporting redox-sensitive activation of phagocytosis in inflammatory macrophages |
| title_full_unstemmed | NAMPT mitigates colitis severity by supporting redox-sensitive activation of phagocytosis in inflammatory macrophages |
| title_short | NAMPT mitigates colitis severity by supporting redox-sensitive activation of phagocytosis in inflammatory macrophages |
| title_sort | nampt mitigates colitis severity by supporting redox sensitive activation of phagocytosis in inflammatory macrophages |
| topic | NAMPT Colitis Macrophage Phagocytic activity NAD+ Inflammatory bowel disease |
| url | http://www.sciencedirect.com/science/article/pii/S221323172200009X |
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