Inflammation
-
Remifentanil significantly represses cell immune responses and influences neutrophil migration through endothelial cell monolayers. The present study determines the beneficial effects of remifentanil and the mechanisms by which it attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI). Rats were intratracheally instilled with 2 mg/kg LPS to induce ALI. ⋯ Remifentanil also attenuated the concentrations of proinflammatory cytokines tumor necrosis factor alpha, interleukin-1β, and interleukin-6 in BALF, as well as effectively repressed the activation of nuclear factor-kappaB (NF-κB), which has been associated with the inhibition of IκBα degradation. These results suggest that remifentanil may be a suitable treatment for LPS-induced ALI. Remifentanil exerts beneficial effects on the inhibition of proinflammatory cytokine production by downregulating the NF-κB pathway.
-
Acute kidney injury-induced organ fibrosis is recognized as a major risk factor for the development of chronic kidney disease, which remains one of the leading causes of death in the developed world. However, knowledge on molecules that may suppress the fibrogenic response after injury is lacking. The long pentraxin 3 (PTX3), a novel acute renal injury marker, has been reported to be involved in chronic renal injury, but the mechanism is still unknown. ⋯ Furthermore, we found that the decreased serum creatinine level and the reduced expression of collagen and smooth muscle actin induced by PTX3 were abolished by additional administration of IL-6. The associated p-Stat3 expression which was reduced by PTX3 administration was also inverted by additional IL-6 treatment. Our data suggest that PTX3 inhibits acute renal injury-induced interstitial fibrosis through suppression of IL-6/Stat3 pathway.
-
The aim of this study was to find serum biomarkers of rheumatoid arthritis (RA) by high-resolution proteomic analysis. Low-abundance proteins from pooling serum sample of early RA patients and healthy controls were enriched using ProteoMiner™ enrichment kits. The enriched proteins were separated on SDS-PAGE, digested by trypsin, labeled with tandem mass tag (TMT) reagents, and desalted by C18 stage tip column. ⋯ Among them, levels of thrombospondin-1, ficolin-2, isoform 10 of fibronectin, and apolipoprotein E were higher in RA patients than in healthy controls (RA/healthy control (HC) ≥ 1.5, p<0.05), while levels of angiotensinogen, paraoxonase/arylesterase 1, isoform E of proteoglycan 4, and plasminogen were significantly lower (RA/HC ≤ 0.67, p<0.05). Further study by ELISA showed a higher level of ficolin-2 in the serum of RA patients compared to healthy controls; the level of ficolin-2 was found to be positively correlated with swollen joint counts (SJCs), disease activity score (DAS28), rheumatoid factor, and IgM in RA patients and with DAS28 and IgM in early RA patients through statistical analysis. The results of this study suggest that ficolin-2, as a newly screened biomarker by high-resolution quantitative proteomic analysis, offers the potentiality to become a diagnostic or disease evaluation tool in RA.
-
The aim of this study was to investigate the potential anti-inflammatory and anti-oxidant effects of gabapentin (GBP) in mice. The anti-inflammatory and anti-oxidant effects were evaluated using various mediators that induce paw edema, peritonitis model, myeloperoxidase (MPO) activity, proinflammatory cytokine levels, glutathione (GSH) consumption, and malondialdehyde (MDA) production in mice. Pretreatment of mice with GBP (1 mg/kg) significantly reduced carrageenan or dextran-induced paw edema (P<0.05) when compared to vehicle group. ⋯ The same dose of GBP also decreased the MDA concentration and increased the levels of GSH into the peritoneal fluid. In summary, our results demonstrated that GBP exhibited anti-inflammatory activity in mice by reducing the action of inflammatory mediators, neutrophil migration and proinflammatory cytokine levels, and anti-oxidant properties by decreasing the concentration of MDA and increasing the GSH content. These observations raise the possibility that GBP could be used to improve tissue resistance to damage during inflammatory conditions.
-
Dexmedetomidine controls systemic cytokine levels through the cholinergic anti-inflammatory pathway.
Previous studies have shown that dexmedetomidine exerted anti-inflammatory effect on several animal models with inflammation, but the mechanism is not clear. This study intends to elucidate the anti-inflammatory mechanism of dexmedetomidine through the cholinergic anti-inflammatory pathway. To investigate this therapeutic potential of dexmedetomidine, a murine model of endotoxemia was established induced by lipopolysaccharide (LPS). ⋯ Our results demonstrate that the preemptive administration of dexmedetomidine increases the activity of cervical vagus nerve and have the ability to successfully improve survival in experimental endotoxemia by inhibiting the inflammatory cytokines release. However, administration of dexmedetomidine to vagotomy or α7 nAChR antagonist pretreatment mice failed to suppress TNF levels, indicating that the vagus nerve and α7nAChR-mediated cholinergic anti-inflammatory pathway is required for the anti-inflammatory effect of dexmedetomidine. These findings show that central alpha-2 agonist dexmedetomidine suppresses systemic inflammation through vagal- and α7nAChR-dependent mechanism.