title: HMGB1 Turns Renal Tubular Epithelial Cells into Inflammatory Promoters by Interacting with TLR4 During Sepsis.
abstract: Our study was undertaken to investigate whether the inflammatory mediator high-mobility group box 1 (HMGB1) can enter the renal tissue and urine and what is the functional change of renal tubular epithelial cells (TECs) interacting with HMGB1 during sepsis. We found that the transcription levels of interleukin 1 (IL-1) and interleukin 6 (IL-6) mRNA in TECs increased significantly during sepsis and these processes can be blocked by splenectomy. We also found out HMGB1 accumulated in the renal tissue and entered urine during sepsis and toll-like receptor 4 (TLR4) was expressed by TECs. In vitro, we demonstrated that HMGB1 induced MAPK and NF-κB activation and G1 cell cycle arrest in TECs. We also found that the mRNA transcription levels of IL-1, IL-6, and tissue inhibitor of metalloproteinases 2 (TIMP2) increased significantly and the IL-1, IL-6, and TIMP2 can be secreted by TECs stimulated by HMGB1. In contrast, LPS RS can block all of the processes above in vitro. In vivo, the increase of the mRNA transcription level of TIMP2 was also observed. These data indicate that HMGB1 accumulates in renal tissue and enters the urine and the interaction between HMGB1 and TLR4 turns TECs into inflammatory promoters during sepsis.
authors: 1 Division of Nephrology, Renmin Hospital of Wuhan University , Wuhan, Hubei, China .
authors: Shixiang
authors: S
authors: Zheng
authors: 1 Division of Nephrology, Renmin Hospital of Wuhan University , Wuhan, Hubei, China .|2 Department of OB/GYN and Women's Health, School of Medicine, University of Louisville , Louisville, Kentucky.
authors: Yangbin
authors: Y
authors: Pan
authors: 3 Division of Critical Care Medicine, Union Hospital of Fujian Medical University , Fuzhou, Fujian, China .
authors: Cairong
authors: C
authors: Wang
authors: 4 Department of Nephrology, Qianfoshan Hospital, Shandong University , Jinan, Shangdong, China .
authors: Yipeng
authors: Y
authors: Liu
authors: 1 Division of Nephrology, Renmin Hospital of Wuhan University , Wuhan, Hubei, China .
authors: Ming
authors: M
authors: Shi
authors: 1 Division of Nephrology, Renmin Hospital of Wuhan University , Wuhan, Hubei, China .
authors: Guohua
authors: G
authors: Ding
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D015398:Signal Transduction; D013156:Splenectomy; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
chemical_list: D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D019716:Tissue Inhibitor of Metalloproteinase-2