PMID- 31591376 OWN - NLM STAT- MEDLINE DCOM- 20200309 LR - 20200309 IS - 1643-3750 (Electronic) IS - 1234-1010 (Print) IS - 1234-1010 (Linking) VI - 25 DP - 2019 Oct 8 TI - Tumor Necrosis Factor-alpha-Induced Protein 8-like 2 Downregulation Reduces CD4(+) T Lymphocyte Apoptosis in Mice with Thermal Injury. PG - 7547-7556 LID - 10.12659/MSM.917229 [doi] AB - BACKGROUND Cellular immunity plays a crucial role in sepsis, and lymphocyte apoptosis is a key factor in immune homeostasis. Tumor necrosis factor-alpha (TNF-alpha)-induced protein 8-like 2 (TIPE2) is suggested to play a critical role in maintaining immune homeostasis. This study investigated the role of TIPE2 in CD4(+) T lymphocyte apoptosis based on a mouse model of thermal injury. MATERIAL AND METHODS BALB/c male mice were randomized into 6 groups: sham, burn, burn with siTIPE2, burn with siTIPE2 control, burn with TIPE2, and burn with TIPE2 control groups. Splenic CD4(+) T lymphocytes were collected by use of a magnetic cell sorting system. RESULTS We found that TIPE2 downregulation reduced the CD4(+) T lymphocytes apoptosis in the burn with siTIPE2 group, and the protein expression of P-smad2/P-Smad3 were remarkably downregulated. In the burn with siTIPE2 group, Bcl-2 expression was increased compared with that in the sham group (P<0.05), and Bim expression was reduced (P<0.05). In the burn with TIPE2 group, the mitochondrial membrane potential was markedly reduced (P<0.01), while cytochrome C expression was clearly higher than that in the other groups (P<0.01). Activities of caspase-3, -8, and -9 were notably higher in the burn with TIPE2 group relative to those for other groups (P<0.05). CONCLUSIONS Downregulation of TIPE2 in vivo can reduce the apoptosis of CD4(+) T lymphocytes following thermal damage, and activate the TGFss downstream signaling of Smad2/Smad3, upregulating Bim, and downregulating Bcl-2. FAU - Huang, He AU - Huang H AD - Department of Critical Care Medicine, The 960th Hospital of the PLA (People's Liberation Army) Joint Logistics Support Force, Jinan, Shandong, China (mainland). FAU - Cui, Yunliang AU - Cui Y AD - Department of Critical Care Medicine, The 960th Hospital of the PLA (People's Liberation Army) Joint Logistics Support Force, Jinan, Shandong, China (mainland). FAU - Tian, Zhaotao AU - Tian Z AD - Department of Critical Care Medicine, The 960th Hospital of the PLA (People's Liberation Army) Joint Logistics Support Force, Jinan, Shandong, China (mainland). FAU - Li, Tanshi AU - Li T AD - Emergency Department, Chinese PLA (People's Liberation Army) General Hospital, Beijing, China (mainland). FAU - Yao, Yongming AU - Yao Y AD - Trauma Research Center, First Hospital Affiliated to the Chinese PLA (People's Liberation Army) General Hospital, Beijing, China (mainland). LA - eng PT - Journal Article DEP - 20191008 PL - United States TA - Med Sci Monit JT - Medical science monitor : international medical journal of experimental and clinical research JID - 9609063 RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (RNA, Small Interfering) RN - 0 (Smad2 Protein) RN - 0 (Smad2 protein, mouse) RN - 0 (Smad3 Protein) RN - 0 (Smad3 protein, mouse) RN - 0 (TIPE2 protein, mouse) RN - 9007-43-6 (Cytochromes c) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Burns/*metabolism/physiopathology MH - CD4-Positive T-Lymphocytes/metabolism MH - Cytochromes c/metabolism MH - Hot Temperature/adverse effects MH - Intracellular Signaling Peptides and Proteins/*metabolism/physiology MH - Male MH - Membrane Potential, Mitochondrial/physiology MH - Mice MH - Mice, Inbred BALB C MH - Models, Animal MH - RNA, Small Interfering/genetics MH - Sepsis/immunology MH - Signal Transduction MH - Smad2 Protein/metabolism MH - Smad3 Protein/metabolism PMC - PMC6795105 EDAT- 2019/10/09 06:00 MHDA- 2020/03/10 06:00 PMCR- 2019/10/08 CRDT- 2019/10/09 06:00 PHST- 2019/10/09 06:00 [entrez] PHST- 2019/10/09 06:00 [pubmed] PHST- 2020/03/10 06:00 [medline] PHST- 2019/10/08 00:00 [pmc-release] AID - 917229 [pii] AID - 10.12659/MSM.917229 [doi] PST - epublish SO - Med Sci Monit. 2019 Oct 8;25:7547-7556. doi: 10.12659/MSM.917229.