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ABSTRACT: Fibroblasts are important to host defence and immunity, can also as initiators of inflammation as well. As the endogenous "braking signal", Lipoxins can regulate anti-inflammation and the resolution of inflammation. We investigated the effect of lipoxinA(4) on the expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts. We demonstrated that the expression of cyclooxygenase-2 protein was significantly increased and peaked initially at 6 hours, with a second increase, with maximal levels occurring 24 hours after lipopolysaccharide challenge. ProstaglandinE(2) levels also peaked at 6 hours, and prostaglandinD(2) levels were increased at both 6 and 24 hours. Exogenous lipoxinA(4) inhibited the first peak of cyclooxygenase-2 expression as well as the production of prostaglandinE(2) induced by lipopolysaccharide in a dose-dependent manner. In contrast, exogenous lipoxinA(4) increased the second peak of cyclooxygenase-2 expression as well as the production of prostaglandinD(2) induced by lipopolysaccharide in a dose-dependent manner. LipoxinA(4) receptor mRNA expression was markedly stimulated by lipopolysaccharide but inhibited by lipoxinA(4). We present evidence for a novel biphasic role of lipoxinA(4) on the expression of cyclooxygenase-2 in lipopolysaccharide-stimulated lung fibroblasts, whereby LXA(4) has an anti-inflammatory and proresolving activity in lung fibroblasts following LPS stimulation.
Mediators of Inflammation 01/2011; 2011:745340. · 3.26 Impact Factor
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ABSTRACT: The histone deacetylase (HDAC) inhibitors have emerged as the useful reagents that epigenetically modulate the expression of various genes. In the present study, the effects of HDAC inhibitors on the expression of inflammation-related genes and lung injury during sepsis were investigated.
Mice were pretreated with two structurally unrelated HDAC inhibitors, Trichostatin A (TSA) and sodium butyrate (SB). Thirty minutes later, mice underwent cecal ligation and puncture (CLP)-induced sepsis. Lung injury and the expression of inflammation-related molecules were determined. In addition, survival was assessed post-CLP.
Our results indicated that administration of TSA or SB alleviated sepsis-induced lung injury. This was accompanied by reduced neutrophil infiltration, decreased intercellular adhesion molecule-1 (ICAM-1) and E-selectin expression in lung tissue, and lower interleukin-6 (IL-6) level in plasma. In addition, treatment with HDAC inhibitors significantly prolonged the survival time of CLP mice.
These data indicated that the HDAC inhibitors, based on modulating the key enzymes linked to acetylation modification, effectively attenuate intrapulmonary inflammatory response, thus significantly alleviating lung injury during sepsis.
World Journal of Surgery 02/2010; 34(7):1676-83. · 2.36 Impact Factor
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ABSTRACT: Background: Lipoxins (LX) are trihydroxytetraene-containing eicosanoids that display unique anti-inflammatory and pro-resolving actions during various inflammatory conditions, but the pathophysiological significance of LX in liver disorders remains unknown. Methods: In the present study, we used a murine model of carbon tetrachloride (CCl(4))-induced acute liver injury to investigate the effects of LX on the progression of acute liver injury. Results: The results indicated that the lipoxin A(4) receptor (ALX) was upregulated after giving CCl(4). BML-111, a commercially available ALX agonist, effectively protected the liver from CCl(4)-induced injury as evidenced by decreased serum aminotransferase (ALT, AST) levels and improved histological damage. The dampened liver injury was accompanied byreduced malondialdehyde (MDA) content in liver homogenates and decreased concentration of tumor necrosis factor-alpha (TNF-alpha) in the serum. Most interestingly, BML-111 markedly upregulated hepatic heme oxygenase-1 (HO-1) expression in CCl(4)-treated mice, which might provide antioxidative activities in the liver. Conclusion: These data indicate that ALX agonist BML-111 plays a critical protective role in CCl(4)-induced acute liver injury through limiting the inflammatory response and promoting antioxidative protein expression.
Hepatology Research 12/2007; 37(11):948-56. · 2.20 Impact Factor
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ABSTRACT: To investigate the protective effect of curcumin on endotoxin-induced acute lung injury in rats, and explore the underlying mechanisms, 24 male Wistar rats were randomly divided into 4 experimental groups: sham-vehicle (S), sham-curcumin (C), lipopolysaccharide (LPS)-vehicle (L), and curcumin-lipopolysaccharide (C-L) groups. The wet/dry (W/D) weight ratio of the lung and bronchoalveolar lavage (BAL) fluid protein content were used as measures of lung injury. Neutrophil recruitment and activation were evaluated by BAL fluid cellularity and myeloperoxidase (MPO) activity in cell-free BAL and lung tissue. The levels of cytokine-induced neutrophil chemoattractant-I (CINC-1) in lung tissues were measured by ELISA. The histopathological changes of lung tissues were observed by using the HE staining. Our results showed that lung injury parameters, including the wet/dry weight ratio and protein content in BALF, were significantly higher in the L group than in the S group (P<0.01). In the L group, higher numbers of neutrophils and greater MPO activity in cell-free BAL and lung homogenates were observed when compared with the S group (P<0.01). There was a marked increase in CINC-1 levels in lung tissues in response to LPS challenge (P<0.01, L group vs S group). Curcumin pretreatment significantly attenuated LPS-induced changes in these indices. LPS caused extensive morphological lung damage, which was also lessened after curcumin pretreatment. All the above-mentioned parameters in the C group were not significantly different from those of the S group. It is concluded that curcumin pretreatment attenuates LPS-induced lung injury in rats. This beneficial effect of curcumin may involves, in part, inhibition of neutrophilic recruitment and activity, possibly through inhibition of lung CINC-1 expression.
Journal of Huazhong University of Science and Technology 01/2006; 26(6):678-81. · 0.38 Impact Factor
