Effect of Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) Blockade in Rats with Cecal Ligation and Puncture (CLP)-Induced Sepsis

Xiaofeng Shi, Yue Zhang, Hao Wang, Sha Zeng
2017 Medical Science Monitor  
Blocking of TREM-1 signaling improves survival of mice with sepsis induced by Pseudomonas aeruginosa. However, whether TREM-1 blockade has beneficial effects in polymicrobial sepsis is poorly understood. Here, we aimed to investigate the effect of modulation of the TREM-1 pathway in rats with polymicrobial sepsis induced by cecal ligation and puncture (CLP). Material/Methods: Normal Sprague-Dawley (SD) rats with sepsis induced by CLP were allocated randomly to received scramble peptide or LP17
more » ... le peptide or LP17 via the jugular vein. Serum level of sTREM-1, IL6, TNF-a, and IL-1b were detected by ELISA assay. The mRNA and protein levels of JAK2 and STAT3 were detected by real-time PCR and Western blot analysis. Results: STREM-1 concentration was greatly and progressively increased in rats with CLP-induced sepsis, and the increase was attenuated by TREM-1 inhibitory peptide LP17. More than 60% survival was observed in rats at the experiment endpoint after LP17 treatment. TREM-1 blockade also attenuated the increased level of pro-inflammatory cytokines TNF-a, IL-6, and IL-1b, and thus attenuated systematic and distant inflammatory responses. Furthermore, TREM-1 blockade significantly attenuated the increased levels of pJAK2 and pSTAT3. Conclusions: TREM-1 blockade by the use of an inhibitory peptide LP17 could prolong survival of rats with polymicrobial sepsis and attenuate systematic inflammatory responses through the JAK2/STAT3 signaling pathway. Our results suggest that modulation of TREM-1 by a synthetic peptide might be a potential therapeutic option for polymicrobial sepsis.
doi:10.12659/msm.904386 fatcat:zysagdtqpfgfzaiy5zu3owzcxy