scholarly journals Transcriptomics Changes in the Peritoneum of Mice with Lipopolysaccharide-Induced Peritonitis

2021 ◽  
Vol 22 (23) ◽  
pp. 13008
Author(s):  
Shaoguang Liu ◽  
Shaotong Zhang ◽  
Yulong Sun ◽  
Wence Zhou

Peritonitis caused by LPS is a severe clinical challenge, which causes organ damage and death. However, the mechanism of LPS-induced peritonitis has not been fully revealed yet. Here, we investigated the transcriptome profile of the peritoneal tissue of LPS-induced peritonitis in mice. A model of LPS-induced peritonitis in mice was established (LPS 10 mg/kg, i.p.), and the influence of TAK 242 (TLR4 inhibitor) on the level of inflammatory cytokines in mouse peritoneal lavage fluid was investigated by using an ELISA test. Next, the peritoneal tissues of the three groups of mice (Control, LPS, and LPS+TAK 242) (n = 6) were isolated and subjected to RNA-seq, followed by a series of bioinformatics analyses, including differentially expressed genes (DEGs), enrichment pathway, protein-protein interaction, and transcription factor pathway. Then, qPCR verified-hub genes that may interact with TAK 242 were obtained. Subsequently, the three-dimensional structure of hub proteins was obtained by using homology modeling and molecular dynamics optimization (300 ns). Finally, the virtual docking between TAK 242 and hub proteins was analyzed. Our results showed that TAK 242 significantly inhibited the production of inflammatory cytokines in the peritoneal lavage fluid of mice with peritonitis, including IL-6, IFN-γ, IL-1β, NO, and TNF-α. Compared with the Control group, LPS treatment induced 4201 DEGs (2442 down-regulated DEGs and 1759 up-regulated DEGs). Compared with the LPS group, 30 DEGs were affected by TAK 242 (8 down-regulated DEGs and 22 up-regulated DEGs). A total of 10 TAK 242-triggered hub genes were obtained, and the possible docking modes between TAK 242 and hub proteins were acquired. Overall, our data demonstrated that a large number of DEGs were affected in LPS-triggered peritonitis mice. Moreover, the TLR4 inhibitor TAK 242 is capable of suppressing the inflammatory response of LPS-induced peritonitis. Our work provides clues for understanding the pathogenesis of LPS-induced peritonitis in mice.

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yan Li ◽  
Hongmei Sun ◽  
Zhiqi Yin ◽  
Xuexi Guo ◽  
Jun Yan

Objective. To investigate the effects of cerium dioxide (CeO2) nanoparticles on the inflammatory response of peritonitis rats induced by Staphylococcus epidermidis infection. Methods. Green tea polyphenol CeO2 nanoparticles were synthesized and characterized by transmission microscopy, ultraviolet-visible spectroscopy, FT-IR, and powder diffractometer. 40 male adult SD rats were randomly divided into 4 groups (n = 10 each): a control group, a model group, a CeO2 group, and a CeO2 + model group. Staphylococcus epidermidis solution was injected intraperitoneally with 107 CFU/ml of bacterial solution in the model group, while the control group was injected intraperitoneally with the same amount of normal saline, and the CeO2 and CeO2 + model groups were injected with 0.5 mg/kg CeO2 nanoparticles through the tail vein for 2 h and then injected with saline or bacterial solution for 2 h, respectively. After 0 h, 3 h, 12 h, 24 h, and 48 h of model construction, rats were sacrificed, and serum and peritoneal lavage fluid were collected. The total number of leukocytes and the percentage of each type of leukocytes in the peritoneal lavage fluid were determined. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of inflammatory factor TNF-α in serum and peritoneal lavage fluid, and myeloperoxidase (MPO) activity in peritoneal tissue was also measured. In addition, real-time fluorescence quantitative PCR (RT-PCR) was used to measure the expression of TLR2 and TLR4 in peritoneal tissue, and western blotting was used to detect the expression of TLR2, TLR4, and the activation of NF-κB signaling pathways as well. Results. The CeO2 has an average size of 37 ± 3 nm with binding activity to proteins, phenolic compounds, and alkaloids. After counting the white blood cells in the peritoneal lavage fluid, it was found that the total number of white blood cells and the percentage of neutrophils in the model group were significantly increased (both P<0.05), and CeO2 treatment significantly reversed the above changes (both P<0.05). The ELISA results showed that compared with the control group, the TNF-α in the peritoneal lavage fluid and serum of the model group increased in a time-dependent manner (all P<0.05); however, there was no significant change in the CeO2 group (P>0.05); at the same time in the CeO2 + model group, the TNF-α content was significantly reduced (all P<0.05). Detection of MPO activity in peritoneal tissue revealed that MPO activity was significantly increased under peritonitis (all P<0.05), and CeO2 treatment could mitigate that increase (all P<0.05). RT-PCR results showed that compared with the control group, the expression of TLR2 and TLR4 mRNA levels in the peritoneum of the model group were increased in a time-dependent manner (all P<0.05), and there was no significant change in the CeO2 group (P>0.05); however, TLR2 and TLR4 mRNA levels were significantly reduced in the CeO2 + model group (all P<0.05). Western blotting test was performed on the peritoneal tissue collected after 48 h of the model establishment. Compared with the control group, the levels of TLR2, TLR4, p–NF–κB, and p-IκBα protein in the model group were significantly increased (all P<0.05), while CeO2 group showed no significant changes (P>0.05) and administration of CeO2 before model construction can significantly reverse the above protein activation (all P<0.05). Conclusion. CeO2 nanoparticles have anti-inflammatory effects in peritonitis caused by Staphylococcus epidermidis infection.


Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 4080-4085 ◽  
Author(s):  
Maria Pini ◽  
Melissa E. Gove ◽  
Joseph A. Sennello ◽  
Jantine W. P. M. van Baal ◽  
Lawrence Chan ◽  
...  

Adipokines, cytokines mainly produced by adipocytes, are active participants in the regulation of inflammation. Administration of zymosan (ZY) was used to investigate the regulation and role of adipokines during peritonitis in mice. Injection of ZY led to a significant increase in leptin levels in both serum and peritoneal lavage fluid, whereas a differential trend in local vs. systemic levels was observed for both resistin and adiponectin. The role of leptin in ZY-induced peritonitis was investigated using leptin-deficient ob/ob mice, with and without reconstitution with exogenous leptin. Leptin deficiency was associated with delayed resolution of peritoneal inflammation induced by ZY, because ob/ob mice had a more pronounced cellular infiltrate in the peritoneum as well as higher and prolonged local and systemic levels of IL-6, TNFα, IL-10, and chemokine (C-X-C motif) ligand 2 compared with wild-type mice. Reconstitution with exogenous leptin exacerbated the inflammatory infiltrate and systemic IL-6 levels in ob/ob mice while inhibiting production of TNFα, IL-10, and chemokine (C-X-C motif) ligand 2. In contrast with the important role of leptin in regulating each aspect of ZY-induced peritonitis, adiponectin deficiency was associated only with a decreased inflammatory infiltrate, without affecting cytokine levels. These findings point to a complex role for adipokines in ZY-induced peritonitis and further emphasize the interplay between obesity and inflammation.


2014 ◽  
Vol 140 (4) ◽  
pp. 607-612 ◽  
Author(s):  
Manabu Yamamoto ◽  
Keiji Yoshinaga ◽  
Ayumi Matsuyama ◽  
Shinichi Tsutsui ◽  
Teruyoshi Ishida

1993 ◽  
Vol 34 (6) ◽  
pp. 829-833 ◽  
Author(s):  
Jonathan H. Jaffin ◽  
M. Gage Ochsner ◽  
Frederic J. Cole ◽  
Grace S. Rozycki ◽  
Mary Kass ◽  
...  

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 4056-4056 ◽  
Author(s):  
M. Takahashi ◽  
F. Kito ◽  
C. Kunisaki ◽  
M. Nomura ◽  
H. Akiyama ◽  
...  

1991 ◽  
Vol 54 (12) ◽  
pp. 917-921 ◽  
Author(s):  
ALAIN MENUDIER ◽  
CLAUDINE BOSIRAUD ◽  
JEAN-ALBERT NICOLAS

Wild strains of Listeria monocytogenes, Listeria ivanovii, Listeria seeligeri, Listeria innocua, and Listeria welshimeri were isolated from infected animals and foodstuffs. Their virulence was tested in Swiss mice after intraperitoneal injection of a fixed number of organisms. The presence of hemolysin was determined using the CAMP test. Bacteria were enumerated in peritoneal lavage fluid, liver, and spleen. Spleen weights were measured, and the presence of L. monocytogenes in the brain was also investigated. L. innocua, L. seeligeri, and L. welshimeri were not found to be pathogenic for mice. L. ivanovii was detected in liver, spleen, and peritoneal lavage fluid but at lower levels than L. monocytogenes (p&lt;0.001). The pathogenic capabilities of four different serovars of L. monocytogenes (4b, 1/2a, 1/2b, 1/2c) were compared. Serovars l/2b and l/2c, which are frequently isolated from foodstuffs, were found to colonize the liver and spleen to a lesser extent than serovar 4b (p&lt;0.01 and &lt;0.001 respectively). The behavior of serovar l/2a, the most commonly isolated from foodstuffs, was strain dependent. Two out of the four strains tested were strongly hemolytic and were as virulent as strains of serovar 4b, while the other two were weakly hemolytic, and avirulent like L. innocua. These results could account for the relatively small number of human Listeria infections due to L. monocytogenes serogroup 1/2, despite the very frequent occurrence of this serovar in foodstuffs.


1992 ◽  
Vol 10 (5) ◽  
pp. 439-444 ◽  
Author(s):  
Dan Tandberg ◽  
Kathy Van Osten ◽  
Paul R. Cheney ◽  
Gerald B. Demarest

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