Inflammation
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Acute kidney injury (AKI) is a severe complication of sepsis, which largely contributes to the high mortality rate of sepsis. Honokiol, a natural product isolated from Magnolia officinalis (Houpo), has been shown to exhibit anti-inflammatory and antioxidant properties. Here, we investigated the effects of honokiol on sepsis-associated AKI in rats subjected to cecal ligation and puncture (CLP). ⋯ The levels of nitric oxide (NO) and inducible NO synthetase (iNOS) were attenuated by honokiol in septic rats. Finally, honokiol inhibited CLP-induced activation of NF-κB signaling in CLP rats. Our findings suggest that honokiol might be used as a potential therapeutic agent for complications of sepsis, especially for sepsis-induced AKI.
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The nucleotide-binding domain leucine-rich repeat proteins (NLRs), a class of innate immune receptors that respond to pathogen attack or cellular stress, have gained increasing attention. NLRC5 is the largest member of NLR family, which has recently been identified as a critical regulator of immune responses. In this study, we explore the role of NLRC5 in cytokine secretion and the role of the JAK2/STAT3 signaling pathway in lipopolysaccharide-induced NLRC5 expression in RAW264.7 cells. ⋯ Meanwhile, AG490 (a specific inhibitor of the JAK2/STAT3 signaling pathway) and JAK2 siRNA were used to manipulate JAK2/STAT3 activity. Finally, the results showed that AG490 and JAK2 siRNA inhibited NLRC5 expression and the expression levels of p-JAK2 and p-STAT3. We, for the first time, demonstrate that the inhibition of the JAK2/STAT3 signaling pathway results in decrease of NLRC5 expression.
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We examined the hypothesis that insulin resistance (IR) decreases circulating concentrations of N-terminal (NT)-probrain natriuretic peptide (BNP). Obesity, despite being a risk factor for heart failure (HF), is paradoxically associated with lower concentrations of BNP, a marker of myocardial stress. Low BNP in obesity is postulated to be due to IR; however, it has been difficult to define the role of IR independent of obesity. ⋯ In a multivariable model adjusted for age, race, and sex, we found that increasing HOMA was statistically associated with increasing NT-proBNP concentrations in RA (P = 0.001), but not controls (P = 0.543) (P for interaction = 0.036). In RA subjects, when IL-6 was further included in the model, IL-6 (P = 0.0014), but not HOMA (P = 0.43), remained significantly associated with NT-proBNP, suggesting that IL-6 may be mechanistically involved in the relationship between IR and NT-proBNP in RA. We conclude that in patients with RA, insulin resistance is associated with higher, rather than the expected lower, concentrations of NT-proBNP and that this may be related to increased IL-6.
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Peritoneal fibrosis is a common consequence of long-term peritoneal dialysis (PD), and peritonitis is a factor in its onset. Agonist-bound peroxisome proliferator-activated receptors (PPARs) function as key regulators of energy metabolism and inflammation. Here, we examined the effects of PPARβ/δ agonist GW501516 on peritonitis in a rat peritoneal fibrosis model. ⋯ Compared to control group, exposure to PD fluids caused peritoneal fibrosis that was accompanied by increased mRNA levels of monocyte chemoattractant protein-1, tumor necrotic factor-α, and interleukin-6 in the uremic rats, and these effects were prevented by GW501516 treatment. Moreover, GW501516 was found to attenuate glucose-stimulated inflammation in cultured rat peritoneal mesothelial cells via inhibition of transforming growth factor-β-activated kinase 1 (TAK1), and nuclear factor kappa B (NFκB) signaling pathway (TAK1-NFκB pathway), a main inflammation regulatory pathway. In conclusion, inhibition of TAK1-NFκB pathway with GW501516 may represent a novel therapeutic approach to ameliorate peritonitis-induced peritoneal fibrosis for patients on PD.
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In the previous study, the anti-inflammatory effect of p-cymene had been found. In this study, we investigated anti-inflammatory effects of p-cymene on acute lung injury using lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. ⋯ The data showed that treatment with the p-cymene markedly attenuated inflammatory cell numbers in the BALF, decreased NF-κB protein level in the lungs, improved SOD activity, and inhibited MPO activity. Histological studies demonstrated that p-cymene substantially inhibited LPS-induced neutrophils in the lung tissue compared with the model group. The results indicated that p-cymene had a protective effect on LPS-induced ALI in mice.