title: Looped limulus anti-lipopolysaccharide derived peptide CLP-19 induces endotoxin tolerance involved inhibition of NF-κB activation.
abstract: Endotoxin tolerance (ET) is a complex protective mechanism against endotoxin shock. The looped CLP-19 peptide derived from Limulus anti-LPS peptide induced the ET phenomenon but the molecular mechanism has yet to be fully elucidated. Here, we confirmed that CLP-19 attenuated upon LPS stimulated pro-inflammatory factor secretion of TNF-α and IL-6 but increased anti-inflammatory factor production of IL-10 in dose- and time-dependent manners. CLP-19 also inhibited subsequent LPS stimulated expression of TLR4 on the cell membrane. Moreover, the CLP-19 inhibited degradation of the inhibitor of NF-κB (IκBα and IκBβ) and reduced LPS induced NF-κB activity, but not of effects on expression of MyD88 and TRAF-6. Finally CLP-19 significantly increased survival of lethal LPS shock mouse models with significantly less pathological injury to lung. These findings collectively suggest that CLP-19 induces ET phenomenon involved inhibition of NF-κB activation. In conclusion, this study has revealed a novel function of CLP-19 that appears to represent a potential therapeutic agent for clinical treatment of septic shock.
authors: Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: swhyangya@163.com.
authors: Ya
authors: Y
authors: Yang
authors: Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Department of Pharmacy, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400038, China. Electronic address: dilee0102@163.com.
authors: Di
authors: D
authors: Li
authors: Department of Immunology, Third Military Medical University, Chongqing 400038, China. Electronic address: tianzq1981@aliyun.com.
authors: Zhiqiang
authors: Z
authors: Tian
authors: Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: lvjun1004@163.com.
authors: Jun
authors: J
authors: Lv
authors: Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: fengj_sun@163.com.
authors: Fengjun
authors: F
authors: Sun
authors: Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: xqwq411@126.com.
authors: Qian
authors: Q
authors: Wang
authors: Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: swhliuyao@163.com.
authors: Yao
authors: Y
authors: Liu
authors: Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: py_xia2013@163.com.
authors: Peiyuan
authors: P
authors: Xia
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage*; D060829:Arthropod Proteins / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology; D004731:Endotoxins / Q000633:toxicity; D008070:Lipopolysaccharides / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D000067996:RAW 264.7 Cells
chemical_list: D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D004731:Endotoxins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C034705:antilipopolysaccharide factor (Limulus)
keywords: CLP-19; Endotoxin tolerance; Immunotherapeutic peptide; Lipopolysaccharide; Nuclear factor-κB