5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice

Abstract

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality. 5-Hydroxytryptamine (5-HT) is an important regulatory factor in inflammation. The aim of this study is to investigate the role of 5-HT on cecal ligation and puncture- (CLP-) induced sepsis in the mouse model. CLP was performed on C57B/6 wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout (KO) mice. The results showed that the 5-HT-sufficient group mice had a significantly lower survival rate than the 5-HT-deficient group in CLP-induced sepsis and septic shock. The KO-CLP sepsis group received a lower clinical score than the WT-CLP sepsis group. Meanwhile, the body temperature of mice in the KO-CLP sepsis group was higher than that in the WT-CLP sepsis group and was much closer to the normal body temperature 24 hours after CLP. The tissue histopathology analysis revealed that 5-HT markedly exacerbated histological damages in the peritoneum, lung, liver, kidney, intestinal tissue, and heart in sepsis. Moreover, significant lower levels of TNF-α, IL-6, bacterial loads, MPO, and ROS were discovered in the KO-CLP sepsis group in contrast to the WT-CLP sepsis group. In conclusion, 5-HT drives mortality and exacerbates organ dysfunction by promoting serum cytokines and bacterial loads as well as facilitating oxidative stress in the process of sepsis.

Irisin alleviates liver ischemia-reperfusion injury by inhibiting excessive mitochondrial fission, promoting mitochondrial biogenesis and decreasing oxidative stress

“…Drp-1 and Fis-1 expression in the liver was detected by immunohistochemical staining. The detailed procedures were conducted as previously described [18] . The primary antibodies rabbit anti-Drp1 antibody (ab184247, Abcam, USA, 1:250 dilution); rabbit anti-Fis1 antibody (Santa Cruz Biotechnology, sc-376447, USA, 1:200 dilution) were incubated overnight at 4 °C, and a secondary antibody (SABC-HRP Kit with Anti-Rabbit IgG, P0615, Beyotime Biotechnology, Shanghai, China, 1:100 dilution) was incubated for 1 h at room temperature.…”

“…Immunofluorescence staining for MPO expression in the liver was performed as previous described [18] The primary antibody rabbit anti-MPO antibody (Santa Cruz Biotechnology, Inc., CA, diluted 1:200) were incubated overnight at 4°. Then the second antibody goat anti-rabbit antibody (Servicebio, China, diluted 1:300) were incubated 50 min at room temperature and counterstained with 4′-6-diamidino-2-phenylindole (DAPI).…”

Functions and Signaling Pathways of Amino Acids in Intestinal Inflammation

“…The best example for EAAs in intestinal inflammation comes from Trp. Trp has a vital role in intestinal inflammation via 5-HT signaling pathway [ 59 ]. 5-HT signaling is made up of tryptophan hydroxylase-1 (TPH-1), 5-HT receptors, and serotonin reuptake transporter (SERT) [ 128 ].…”

Azithromycin in Combination with Ceftriaxone Reduces Systemic Inflammation and Provides Survival Benefit in a Murine Model of Polymicrobial Sepsis

“…S epsis is characterized by life-threatening organ dysfunction, in which the proinflammatory cytokines released by host immune cells in response to infection play a major role in pathogenesis (1,2). In septic patients, there is an imbalance of proinflammatory/anti-inflammatory and oxidant/antioxidant mechanisms, resulting in the uncontrolled production of proinflammatory cytokines (e.g., interleukin-1␤ [IL-1␤], IL-6, and tumor necrosis factor alpha [TNF-␣]), oxidative enzymes (e.g., myeloperoxidase [MPO]), and free oxygen species that induce oxidative stress, inflammation, and direct mitochondrial damage, precipitating to organ dysfunction (3,4,5). Despite recent advances in our understanding of the pathophysiological mechanism of sepsis and improved antimicrobial therapy, the rate of mortality from sepsis remains frustratingly high (6).…”