RESUMEN
Sepsis, a life-threatening condition caused by infection, is characterized by the dysregulation of immune responses and activation of monocytes. Plac8, a protein, has been implicated in various inflammatory conditions. This study aimed to investigate the effect of Plac8 upregulation on monocyte proliferation and activation in sepsis patients. Peripheral blood samples were collected from healthy individuals and sepsis patients. Monocytes were stimulated with lipopolysaccharide (LPS) to create an in vitro sepsis model, while a murine sepsis model was established using cecal ligation and puncture (CLP). The levels of monocyte markers, proliferation index (PI), and pro-inflammatory cytokines were assessed using flow cytometry and qPCR, respectively. Plac8 and phosphorylated ERK protein levels were determined by western blot, and TNF-α, IL-6, and IL-10 levels were quantified using ELISA. The CCK-8 assay was used to evaluate PBMC proliferation and activation. The results showed that Plac8 was highly expressed in sepsis models, promoting the survival, proliferation, and activation of monocytes. Plac8 upregulation activated the ERK pathway, leading to increased phosphorylation of ERK protein and elevated levels of CD14, CD16, TNF-α, IL-6, Plac8, and IL-10. In sepsis mice, Plac8 overexpression similarly activated the ERK pathway and promoted the survival, proliferation, and activation of monocytes. In conclusion, the upregulation of Plac8 enhances the activation of the ERK pathway and promotes monocyte proliferation and activation in sepsis patients.
RESUMEN
BACKGROUND: The induction of intestinal inflammation as a result of abdominal surgery is an essential factor in postoperative ileus (POI) development. Electroacupuncture (EA) at ST36 has been demonstrated to relieve intestinal inflammation and restore gastrointestinal dysmotility in POI. This study aims to elucidate the neuroimmune pathway involved in the anti-inflammatory properties of EA in POI. METHODS: After intestinal manipulation (IM) was performed to induce POI, intestinal inflammation and motility were assessed 24â¯h post-IM, by evaluating gastrointestinal transit (GIT), cytokines expression, and leukocyte infiltration. Experimental surgery, pharmacological intervention, and genetic knockout mice were used to elucidate the neuroimmune mechanisms of EA. RESULTS: EA at ST36 significantly improved GIT and reduced the expression of pro-inflammatory cytokines and leukocyte infiltration in the intestinal muscularis following IM in mice. The anti-inflammatory effectiveness of EA treatment was abolished by sub-diaphragmatic vagotomy, whereas splenectomy did not hinder the anti-inflammatory benefits of EA treatment. The hexamethonium chloride (HEX) administration contributes to a notable reduction in the EA capacity to suppress inflammation and enhance motility dysfunction, and EA is ineffective in α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice. CONCLUSIONS: EA at ST36 prevents intestinal inflammation and dysmotility through a neural circuit that requires vagal innervation but is independent of the spleen. Further findings revealed that the process involves enteric neurons mediating the vagal signal and requires the presence of α7nAChR. These findings suggest that utilizing EA at ST36 may represent a possible therapeutic approach for POI and other immune-related gastrointestinal diseases.
