Fusobacterium nucleatum-Induced Impairment of Autophagic Flux Enhances the Expression of Proinflammatory Cytokines via ROS in Caco-2 Cells.
Fusobacterium nucleatum (F. nucleatum) plays a critical role in gastrointestinal inflammation. However, the exact mechanism by which F. nucleatum contributes to inflammation is unclear. In the present study, it was revealed that F. nucleatum could induce the production of proinflammatory cytokines (IL-8, IL-1β and TNF-α) and reactive oxygen species (ROS) in Caco-2 colorectal) adenocarcinoma cells. Furthermore, ROS scavengers (NAC or Tiron) could decrease the production of proinflammatory cytokines during F. nucleatum infection. In addition, we observed that autophagy is impaired in Caco-2 cells after F. nucleatum infection. The production of proinflammatory cytokines and ROS induced by F. nucleatum was enhanced with either autophagy pharmacologic inhibitors (3-methyladenine, bafilomycin A1) or RNA interference in essential autophagy genes (ATG5 or ATG12) in Caco-2 cells. Taken together, these results indicate that F. nucleatum-induced impairment of autophagic flux enhances the expression of proinflammatory cytokines via ROS in Caco-2 Cells.
Department of Clinical Microbiology and Immunology, Southwest Hospital & College of Medical Laboratory Science, Third Military Medical University, Chongqing, China.|Emei Sanatorium of PLA Rocket Force, Emeishan, China.
Bin
B
Tang
Department of Clinical Microbiology and Immunology, Southwest Hospital & College of Medical Laboratory Science, Third Military Medical University, Chongqing, China.
Kun
K
Wang
Department of Clinical Microbiology and Immunology, Southwest Hospital & College of Medical Laboratory Science, Third Military Medical University, Chongqing, China.
Yin-Ping
YP
Jia
Department of Clinical Microbiology and Immunology, Southwest Hospital & College of Medical Laboratory Science, Third Military Medical University, Chongqing, China.
Pan
P
Zhu
Department of Clinical Microbiology and Immunology, Southwest Hospital & College of Medical Laboratory Science, Third Military Medical University, Chongqing, China.
Yao
Y
Fang
Department of Clinical Microbiology and Immunology, Southwest Hospital & College of Medical Laboratory Science, Third Military Medical University, Chongqing, China.
Zhu-Jun
ZJ
Zhang
Department of Clinical Microbiology and Immunology, Southwest Hospital & College of Medical Laboratory Science, Third Military Medical University, Chongqing, China.
Xu-Hu
XH
Mao
Department of Clinical Microbiology and Immunology, Southwest Hospital & College of Medical Laboratory Science, Third Military Medical University, Chongqing, China.
Qian
Q
Li
Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
Dong-Zhu
DZ
Zeng
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000111:Acetylcysteine / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D000071192:Autophagy-Related Protein 12 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D000071187:Autophagy-Related Protein 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005674:Fusobacterium Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016967:Fusobacterium nucleatum / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology*; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*
C466624:ATG12 protein, human; C502778:ATG5 protein, human; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D016166:Free Radical Scavengers; C508585:IL1B protein, human; D053583:Interleukin-1beta; D016209:Interleukin-8; D018942:Macrolides; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; C025946:3-methyladenine; C040929:bafilomycin A1; D000225:Adenine; D000111:Acetylcysteine