https://kumel.medlib.dsmc.or.kr/handle/2015.oak/29778 Sat, 04 Apr 2026 20:12:13 GMT 2026-04-04T20:12:13Z https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46554 Title: ATG7 in innate immune cells is required for host defense against nontuberculous mycobacterial pulmonary infections Author(s): Sang Min Jeon; Yeon Ju Lee; Sang-Hee Lee; Soo In Kim; Bomi Lee; Taylor Roh; Young Jae Kim; Hyeon Ji Kim; In Soo Kim; Jake Whang; So-Young Kim; Byung Woo Jhun; Chaeuk Chung; Da Hyun Kang; Min-Kyung Yeo; Jin-Man Kim; Jichan Jang; Jung-Joon Min; Masaaki Komatsu; Jin Kyung Kim; Woong-Yang Park; Eun-Kyeong Jo Abstract: Infections caused by nontuberculous mycobacteria, such as Mycobacterium avium and Mycobacteroides abscessus, are becoming increasingly prevalent, and rising antibiotic resistance poses a significant clinical challenge. However, the mechanisms by which the host defense system controls these infections remain poorly understood. Here we show that the autophagy-related protein ATG7 in innate immune cells plays an essential role in controlling nontuberculous mycobacterial infection and protecting lung tissue from pathological inflammation. Patients with nontuberculous mycobacterial pulmonary disease exhibit reduced ATG7 expression in blood mononuclear cells and decreased ATG7 levels in necrotic lesions at disease sites. Mice lacking Atg7 in innate immune cells display elevated bacterial loads, excessive inflammation, mitochondrial damage, and multiple forms of cell death in the lungs, including pyroptosis, necrosis, and apoptosis. Notably, neutrophil infiltration in the lungs of these mice plays a key role in driving exacerbated inflammation and gasdermin E-associated cell death, which precede bacterial overgrowth. In vitro, Atg7-deficient macrophages exhibit impaired antimicrobial responses and reduced phagolysosomal fusion, but only modest increases in inflammation and cell death. These findings underscore the critical role of ATG7 in innate immune cells in orchestrating an effective host defense against nontuberculous mycobacterial lung infection by mitigating neutrophil-driven pathological inflammation and associated cell death. Tue, 31 Dec 2024 15:00:00 GMT https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46554 2024-12-31T15:00:00Z https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46227 Title: Chaetocin enhances tumor necrosis factor‑related apoptosis‑inducing ligand‑mediated apoptosis by enhancing DR5 stabilization and reactive oxygen species generation in human glioblastoma cells Author(s): Hui-Jung Jung; Jin Kyung Kim; Seong-Il Suh; Won-Ki Ba다 Abstract: Chaetocin, a fungal metabolite, exerts notable antiproliferative effects against solid tumors by triggering apoptosis; however, the mechanisms underlying its effects remain unclear. As tumor necrosis factor (TNF)‑related apoptosis‑inducing ligand (TRAIL) promotes apoptosis in certain types of tumor, the present study aimed to explore the sensitizing effects of chaetocin in TRAIL‑induced apoptosis in human glioblastoma cells and the underlying mechanism. Human glioblastoma cells (U343MG, U87MG, U251MG, and T98G) and embryonic kidney cells (HEK293) were co‑treated with chaetocin and TRAIL, followed by assessment of cell viability. The results from viability and apoptosis assays demonstrated a significant increase in caspase-dependent apoptosis in glioblastoma cells, but not in HEK293 cells, upon co-treatment with chaetocin and TRAIL. Additionally, death receptor 5 (DR5) expression analysis demonstrated that co‑treatment with chaetocin and TRAIL upregulated DR5 expression in a dose‑ and time‑dependent manner by increasing the stability of DR5 on the cell surface. In glioblastoma cells, small interfering RNA‑mediated DR5 knockdown markedly suppressed chaetocin/TRAIL‑induced apoptosis. Moreover, chaetocin enhanced reactive oxygen species (ROS) production, which facilitated TRAIL‑mediated apoptosis by enhancing DR5 upregulation. Thus, chaetocin sensitized the human glioblastoma cell lines U87MG and T98G to TRAIL‑mediated apoptosis by upregulating DR5 expression through ROS-mediated mechanisms. The present findings underscore chaetocin as a potential novel therapeutic agent for glioblastoma. Tue, 31 Dec 2024 15:00:00 GMT https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46227 2024-12-31T15:00:00Z https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46037 Title: The intricate interactions between inflammasomes and bacterial pathogens: Roles, mechanisms, and therapeutic potentials Author(s): Jin Kyung Kim; Asmita Sapkota; Taylor Roh; Eun-Kyeong Jo Abstract: 4-HNE4-hydroxynonenalAIM2absent in melanoma 2ALIacute lung injuryAMPKAMP-activated protein kinaseASCapoptosis-associated speck-like protein containing a caspase recruitment domainATPadenosine triphosphateCARDcaspase recruitment domainCARDScommunity-acquired respiratory distress syndromeCDClostridioides difficileCGRPcalcitonin gene-related peptidecryo-EMcryo-electron microscopyERendoplasmic reticulumFMFFamilial Mediterranean feverGASGroup A StreptococcusGBPsguanylate-binding proteinsGSDMDgasdermin DHDACshistone deacetylaseshGBPhuman GBP1IECsintestinal epithelial cellsIFN-γinterferon-γILinterleukinIFN-Itype I IFNJNKJun N-terminal kinaseKOknockoutKPKlebsiella pneumoniaeLLOlisteriolysin OLMListeria monocytogenesLncenc1long noncoding RNA embryonic stem cells expressed 1lncRNAlong noncoding RNALPLegionella pneumophilaLPSlipopolysaccharideLRRleucine-rich repeatLTlethal toxinMAMsmitochondria-associated membranesMDA5melanoma differentiation factor 5MDRmultidrug resistantMEG3–4maternally expressed gene 3 transcript 4miRNAsmicroRNAsMLKLmixed lineage kinase-likeMtbMycobacterium tuberculosismtDNAmitochondrial DNAmtROSmitochondrial reactive oxygen speciesNAIPsneuronal apoptosis inhibitory proteinsNCOA6nuclear receptor coactivator 6NEK7NIMA-related kinase 7NF-κBnuclear factor-κBNLRCsnucleotide-binding oligomerization domain-like receptor C proteinsNLRPsnucleotide-binding oligomerization domain-like receptorsNLRsNOD-like receptorsNODnucleotide oligomerization domainNSPsneutrophil serine proteasesOMVsouter membrane vesiclesPAPseudomonas aeruginosaPakp21-activated kinasesPAMPspathogen-associated molecular patternsPDHKpyruvate dehydrogenase kinaseRIPKreceptor interacting serine/threonine kinasePKCδprotein kinase C-deltaROSreactive oxygen speciesPRKprotein kinase C-like kinasePTMposttranslational modificationPYDpyrin domainSARS-CoV-2severe acute respiratory syndrome coronavirus 2SPI-1Salmonella pathogenicity island 1STINGstimulator of interferon genesSTECShiga-toxigenic E. coliSUMOsmall ubiquitin-like modifierThT helperT3SStype 3 secretion systemT4SStype IV secretion systemTLRtoll-like receptorTNFtumor necrosis factorTREM2triggering receptors expressed on myeloid cells 2TRIFTIR domain-containing adapter moleculeTRIM28tripartite motif-containing protein 28WTwild-typeXISTX inactivate-specific transcriptZAKαleucin-zipper and sterile-α motifZbp1Z-DNA-binding protein 1 Tue, 31 Dec 2024 15:00:00 GMT https://kumel.medlib.dsmc.or.kr/handle/2015.oak/46037 2024-12-31T15:00:00Z https://kumel.medlib.dsmc.or.kr/handle/2015.oak/45922 Title: Ubiquitin regulatory X (UBX) domain-containing protein 6 is essential for autophagy induction and inflammation control in macrophages Author(s): Young Jae Kim; Sung-Gwon Lee; So Young Park; Sang Min Jeon; Soo In Kim; Kyung Tae Kim; Taylor Roh; Sang-Hee Lee; Min Joung Lee; Jinyoung Lee; Hyeon Ji Kim; So Eui Lee; Jin Kyung Kim; Jun Young Heo; In Soo Kim; Chungoo Park; Seungwha Paik; Eun-Kyeong Jo Abstract: Ubiquitin regulatory X (UBX) domain-containing protein 6 (UBXN6) is an essential cofactor for the activity of the valosin-containing protein p97, an adenosine triphosphatase associated with diverse cellular activities. Nonetheless, its role in cells of the innate immune system remains largely unexplored. In this study, we report that UBXN6 is upregulated in humans with sepsis and may serve as a pivotal regulator of inflammatory responses via the activation of autophagy. Notably, the upregulation of UBXN6 in sepsis patients was negatively correlated with inflammatory gene profiles but positively correlated with the expression of Forkhead box O3, an autophagy-driving transcription factor. Compared with those of control mice, the macrophages of mice subjected to myeloid cell-specific UBXN6 depletion exhibited exacerbated inflammation, increased mitochondrial oxidative stress, and greater impairment of autophagy and endoplasmic reticulum-associated degradation pathways. UBXN6-deficient macrophages also exhibited immunometabolic remodeling, characterized by a shift to aerobic glycolysis and elevated levels of branched-chain amino acids. These metabolic shifts amplify mammalian target of rapamycin pathway signaling, in turn reducing the nuclear translocation of the transcription factor EB and impairing lysosomal biogenesis. Together, these data reveal that UBXN6 serves as an activator of autophagy and regulates inflammation to maintain immune system suppression during human sepsis. Sun, 31 Dec 2023 15:00:00 GMT https://kumel.medlib.dsmc.or.kr/handle/2015.oak/45922 2023-12-31T15:00:00Z