title: TRIM22-Mediated Apoptosis is Associated with Bak Oligomerization in Monocytes.
abstract: Monocyte apoptosis is a key mechanism that orchestrates host immune responses during sepsis. TRIM22 is constitutively expressed at high levels in monocytes and plays important roles in the antiviral response and inflammation. Overexpression of TRIM22 interferes with the clonogenic growth of monocytic cells, suggesting that TRIM22 may regulate monocyte survival. However, the effect of TRIM22 on monocyte apoptosis remains unknown. In the present report, lipopolysaccharides (LPS)-primed human peripheral blood monocytes expressing higher levels of TRIM22 were more sensitive to apoptosis. This phenomenon was also observed in TRIM22-overexpressing THP-1 monocytes and was associated with the activation of caspase-9 and caspase-3, as well as the increased expression and oligomerization of the pro-apoptotic protein Bak. Similar expression patterns of TRIM22 and Bak were also observed in LPS-primed, apoptotic human peripheral blood monocytes. In addition, the deletion of either the RING domain or the SPRY domain of TRIM22 significantly attenuated TRIM22-mediated monocyte apoptosis and decreased Bak expression and oligomerization. Furthermore, in monocytes from septic patients, TRIM22 levels were down-regulated and positively correlated with Bak levels. Taken together, these results indicate that TRIM22 plays a critical role in monocyte apoptosis by regulating Bak oligomerization and may have a potential function in the pathogenesis of sepsis.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Children's Hospital, School of Medicine, Zhejiang University, and Zhejiang Key Laboratory for Diagnosis and Therapy of Neonatal Diseases, Hangzhou 310052, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Children's Hospital, School of Medicine, Zhejiang University, and Zhejiang Key Laboratory for Diagnosis and Therapy of Neonatal Diseases, Hangzhou 310052, China.
authors.forename: DongYan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Children's Hospital, School of Medicine, Zhejiang University, and Zhejiang Key Laboratory for Diagnosis and Therapy of Neonatal Diseases, Hangzhou 310052, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Fang
authors.affiliation: Clinical Research Center, Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China.
authors.forename: QiXing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: BaoLi
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: XiangMing
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Children's Hospital, School of Medicine, Zhejiang University, and Zhejiang Key Laboratory for Diagnosis and Therapy of Neonatal Diseases, Hangzhou 310052, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shu
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D000071197:B30.2-SPRY Domain / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055503:Protein Multimerization; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism / Q000473:pathology; D000070584:Tripartite Motif Proteins / Q000235:genetics / Q000378:metabolism*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D015778:Minor Histocompatibility Antigens; D012097:Repressor Proteins; C094314:TRIM22 protein, human; D000070584:Tripartite Motif Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D053148:Caspase 3; D053453:Caspase 9