PMID- 15489642
OWN - NLM
STAT- MEDLINE
DCOM- 20050324
LR  - 20190917
IS  - 1073-2322 (Print)
IS  - 1073-2322 (Linking)
VI  - 22
IP  - 5
DP  - 2004 Nov
TI  - Role of chemically modified tetracycline on TNF-alpha and mitogen-activated 
      protein kinases in sepsis.
PG  - 478-81
AB  - Chemically modified tetracyclines are orally active inhibitors of multiple 
      proteases and cytokines. In this study, we focused on the regulation of tumor 
      necrosis factor (TNF)-alpha and mitogen-activated protein kinases (MAPKs) in 
      sepsis and their reduction by treatment with nonantimicrobial chemically modified 
      tetracycline-3 (CMT-3), which retains their antiinflammatory activity. Sepsis was 
      induced in rats by cecal ligation and puncture (CLP). At 24 h and 1 h before CLP, 
      treated rats received CMT-3 (25 mg/kg), and untreated rats received saline by 
      gavage. At 0 h, 0.5 h, 1.5 h, and 24 h after CLP, blood and liver samples were 
      collected. TNF-alpha was determined by ELISA, and MAPKs were determined by 
      Western blot analysis. A significant activation of p38 MAPK was observed after 
      0.5 h and 1.5 h of sepsis that appeared to coincide with the increased 
      circulating TNF-alpha level. The activation of p42/44 was increased after 24 h of 
      sepsis, whereas that of SAPK/JNK was unaltered throughout the course of sepsis. 
      CMT-3 pretreatment inhibited the TNF-alpha level as well as p38 MAPK activation 
      seen after 0.5 and 1.5 h of CLP and also suppressed the activation of p42/44 
      after 24 h post-CLP. These results indicate increased activity of TNF-alpha and 
      MAPK following sepsis and demonstrate the beneficial effect of CMT-3 in 
      preventing the increase in TNF-alpha, p38 MAPK, p42/44 MAPK, and the progression 
      of septic shock.
FAU - Maitra, Subir R
AU  - Maitra SR
AD  - Trauma Research Laboratory, Department of Emergency Medicine, School of Medicine, 
      State University of New York, Stony Brook, NY 11794-7400, USA. 
      smaitra@notes.cc.sunysb.edu
FAU - Bhaduri, Sikha
AU  - Bhaduri S
FAU - Chen, Elliott
AU  - Chen E
FAU - Shapiro, Marc J
AU  - Shapiro MJ
LA  - eng
GR  - R01GM58047/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Cytokines)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Tetracyclines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - F8VB5M810T (Tetracycline)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cytokines/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Liver/enzymology
MH  - *MAP Kinase Signaling System
MH  - Male
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Protein Synthesis Inhibitors/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Sepsis/enzymology
MH  - Tetracycline/chemistry/*pharmacology
MH  - Tetracyclines/*pharmacology
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/*chemistry
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2004/10/19 09:00
MHDA- 2005/03/25 09:00
CRDT- 2004/10/19 09:00
PHST- 2004/10/19 09:00 [pubmed]
PHST- 2005/03/25 09:00 [medline]
PHST- 2004/10/19 09:00 [entrez]
AID - 00024382-200411000-00013 [pii]
AID - 10.1097/01.shk.0000140298.40440.51 [doi]
PST - ppublish
SO  - Shock. 2004 Nov;22(5):478-81. doi: 10.1097/01.shk.0000140298.40440.51.