Protective effect of capsaicin on lipopolysaccharide-induced activation of vascular endothelial cells

AIM:To investigate the effect of capsaicin on lipopolysaccharide (LPS)-induced activation of cultured endothelial cells of mouse aorta in vitro. METHODS:The endothelial cells were isolated from mouse aorta and cultured in vitro, and the specific cell markers of the cells were identified by immunofluorescence staining. The cells were stimulated with LPS (100 μg/L) combined with or without capsaicin, and the cells and supernatant were collected at 12 h, 24 h and 48 h. The levels of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1) and soluble P-selectin (sP-selectin) in the supernatant were measured by ELISA. The levels of nuclear NF-κB p65 and cytopasmic p-IκBα and IκBα were detected by Western blotting. RESULTS:Compared with control group, the levels of sP-selectin, sICAM-1 and sVCAM-1 in LPS group were significantly increased (P<0.05), and LPS promoted the expression of sICAM-1 and sVCAM-1 in a time-dependent manner. Compared with LPS group at the same time point, capsaicin inhibited the expression of sP-selectin, sICAM-1 and sVCAM-1 in a dose-dependent manner. Compared with control group, the protein levels of NF-κB p65 and p-IκBα in LPS group at 24 h were significantly increased (P<0.05), while the protein level of IκBα in LPS group at 24 h were significantly decreased (P<0.05). Compared with LPS group, capsaicin decreased the protein levels of NF-κB p65 and p-IκBα and increased the protein level of IκBα in a dose-dependent manner. CONCLUSION: Capsaicin has a protective effect on LPS-induced vascular endothelial cell activation, which potentially contributes to the suppression of IκBα degradation and NF-κB p65 nuclear translocation.     

1,25-dihydroxyvitamin D3 inhibits nuclear factor kappa B signaling pathway in passively sensitized human airway smooth muscle cells

AIM:To investigate the effects of 1,25-dihydroxyvitamin D3 ［1,25-(OH)2D3］ on nuclear factor kappa B (NF-κB) signaling pathway in passively sensitized human airway smooth muscle cells (HASMCs). METHODS:HASMCs were passively sensitized with 10% serum from asthmatic patients. 1,25-(OH)2D3 was used as an interfering factor. Electrophoretic mobility shift assay (EMSA) was used to detect the DNA-binding activity of NF-κB. Immunocytochemical staining was used to observe the nuclear translocation of NF-κB p65. Western blotting was used for IκBα and phosphorylated IκBα protein detection. Real-time fluorescence quantitative PCR was used to determine vitamin D receptor (VDR), vitamin D 24-hydroxylase (CYP24) and IκBα mRNA expression. The mRNA expression of IκBα in HASMCs after actinomycin D treatment was also determined. RESULTS:(1) 1,25-(OH)2D3 significantly attenuated the DNA-binding activity of NF-κB and the nuclear translocation of NF-κB p65 in HASMCs passively sensitized by asthmatic serum. (2) 1,25-(OH)2D3 enhanced IκBα mRNA stability and inhibited IκBα protein phosphorylation in passively sensitized HASMCs, thus increasing IκBα expression in these HASMCs. (3) 1,25-(OH)2D3 up-regulated VDR mRNA level and evoked its functional response in passively sensitized HASMCs. CONCLUSION: 1,25-(OH)2D3 enhanced the expression of IκBα and therefore inhibited NF-κB signaling passway in HASMCs. This effect may be dependent on VDR, and responsible for the inhibitory effect of 1,25-(OH)2D3 on passively sensitized HASMCs.     

Resveratrol attenuates inflammatory pain induced by complete Freund's adjuvant via NF-κB signaling pathway in a mouse model

AIM: To investigate the anti-inflammatory action of resveratrol (Res) and its correlation with nuclear factor-κB (NF-κB) signaling pathway in a mouse model of inflammatory pain.METHODS: BALB/c mice (n=60) were randomly divided into 6 groups:normal control group, inflammatory pain model group, positive control (dexamethasone, 0.5 mg/kg) group and resveratrol (100, 50 and 25 mg/kg) groups (10 mice in each group). In order to observe the anti-inflammatory pain effects of reseratrol on mice, the paw withdrawal mechanical threshold, paw withdrawal thermal latency and cold withdrawal times were detected. In order to analyze the mechanism of analgesic effect of resveratrol, the expression levels of NF-κB, inhibitor of NF-κB (IκB) α, inhibitor of NF-κB kinase (IKK) β, tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the spinal cord tissues (L4~L6) of the mice were determined by RT-PCR and Western blot.RESULTS: The resveratrol at 100 and 50 mg/kg increased the paw withdrawal mechanical threshold, prolonged the paw withdrawal thermal latency, and decreased the cold withdrawal times in the inflammatory pain mice (P<0.05 or P<0.01). The resveratrol at 100 mg/kg down-regulated the mRNA and protein expression levels of NF-κB, IκBα, IKKβ, TNF-α and IL-1β in the spinal cord tissues (L4~L6) of inflammatory pain mice (P<0.05 or P<0.01).CONCLUSION: Resveratrol ameliorates the inflammatory pain of the mice induced by complete Freund's adjuvant. The mechanism is related to the inhibition of NF-κB signaling pathway.     

Effects of diterpenoid C from ether extract of Radix Curcumae on nuclear factor-κB activity in LPS-induced human gastric adenocarcinoma SGC7901 cells

AIM: To observe the effects of diterpenoid C from ether extract of Radix Curcumae (RC) on the activity of nuclear factor-κB in human gastric adenocarcinoma SGC7901 cells stimulated with lipopolysaccharide (LPS). METHODS: SGC7901 cells were normally cultured, induced by LPS, or treated with LPS plus RC. The protein expression of IKKα, IKKβ, p65, phosphorylated p65 and phosphorylated IκBα was assayed by Western blotting. NF-κB DNA binding activity was determined by electrophoretic mobility shift assay. RESULTS: RC reduced the protein expression of IKKα, IKKβ, p65, phosphorylated p65 and phosphorylated IκBα induced by LPS. NF-κB DNA binding activity increased much greatly by LPS stimulation, while RC resisted the action of LPS. CONCLUSION: RC may attenuate the secretion of inflammatory cytokines by inhibiting the activation of NF-κB signaling pathway.     

Linarin inhibits migration and invasion abilities of human breast cancer MDA-MB-231 cells through IKK/NF-κB signaling pathway

AIM: To investigate the effect of linarin (LIN) on the migration and invasion abilities of human breast cancer MDA-MB-231 cells and its underlying mechanism. METHODS: MCF-7, MDA-MB-231 and MCF-10A cells were cultured in vitro and treated with LIN at 5, 10, 20, 40, 80 and 160 μmol/L for 24 h, and the cell proliferation was measured by CCK-8 assay and colony formation assay. The protein levels of Snail, E-cadherin, matrix metalloproteinase-9 (MMP-9), IκBα, p-IKKα/β and p-p65 were determined by Western blot. RESULTS: LIN remarkably reduced the viability of MDA-MB-231 cells in a dose-dependent manner (P<0.05), and the IC₅₀ was 55.89 μmol/L for 24 h. LIN decreased the colony formation rate of MDA-MB-231 cells at the concentration of 20 μmol/L (P<0.05). After exposed to LIN at 5 μmol/L and 10 μmol/L for 24 h, the migration and invasion abilities of the MDA-MB-231 cells were significantly reduced (P<0.05), the protein expression levels of E-cadherin and IκBα were up-regulated (P<0.05), the protein expression levels of Snail and MMP-9 were down-regulated (P<0.05), and the phosphorylation levels of IKKα/β and p65 were decreased (P<0.05) in comparison with the control group. Meanwhile, IKK-16 (IKKα/β inhibitor) and PDTC (NF-κB inhibitor) also down-regulated the protein expression levels of Snail and MMP-9 (P<0.05), and up-regulated the protein expression level of E-cadherin (P<0.05). CONCLUSION: LIN down-regulates the protein expression levels of Snail and MMP-9, and up-regulates the protein expression level of E-cadherin most likely through inhibiting IKK/NF-κB signaling pathway, and ultimately lead to decreases in the migration and invasion abilities of MDA-MB-231 cells.     

Advances in IκB protein family research

IκB is an inhibitor of nuclear factor-kappa B (NF-κB) and presents in the majority of cells. Eight structurally related members of the mammalian IκB family have been described:IκBα, IκBβ, IκBε, Bcl-3, IκBγ, IκBδ, p100 and p105. The ankyrin repeat domain of IκB can interact with NF-κB, and sequester NF-κB in the cytoplasm as inactive complexes. Most recently, IκBα has been found to inhibit p53 tumor suppressor protein by binding p53 to form a cytoplasmic p53·IκBα complex and studies have shown that p100 profoundly sensitizes cells to death-receptor-mediated apoptosis. The current review is to describe the members of IκB family, their related signaling pathways, and their application in tumor therapy.     

Effects of burn sera on IκBα degradation and NF-κB activation in monocytes in vitro

AIM: To investigate the effects of burn sera on IκBα degradation, NF-κB activation in peripheral blood monocytes (PBMCs) in order to explore the role of burn sera on activation of monocytes. METHODS: PBMCs isolated from healthy volunteers were stimulated by sera from healthy volunteers and burn patients and by burn sera together with PDTC (pyrrolidine dithioncarbamate). Activation of monocytic NF-κB was tested by electrophoretic mobility shift assay (EMSA) and the degradation of monocytic IκBα was determined by Western blotting. RESULTS: When compared to that in control group, cytosolic IκBα degradation occurred within 30 min after PBMCs stimulated by burn sera, and peaked at 60 min. But IκBα gradually recovered in the cytoplasm after 2 h of stimulation. Meanwhile, activity of monocytic NF-κB was markedly increased, reached the peak at 30 min to 60 min after stimulation, and gradually decreased after 2 h of stimulation. PDTC (an antioxidants) effectively inhibited the monocytic IκBα degradation and activation of NF-κB induced by burn sera. CONCLUSION: Burn sera might induce the degradation of IκBα, then activate NF-κB, which ultimately lead to the secretion of cytokines from the monocytes.     

Effects of Jiedu-Qingfei mixture on NF-κB and p38 MAPK pathways in lung tissues of rats with Mycoplasma pneumoniae infection

AIM: To observe the therapeutic effect of Jiedu-Qingfei mixture on Mycoplasma pneumoniae (MP)-infected rat lung tissues and to explore its mechanism. METHODS: SD rats (n=40) were randomly divided into 4 groups:blank control group, model group, Jiedu-Qingfei group and positive control group, with 10 rats in each group. The rats in experimental groups were slowly dripped with 1×10⁹ CFU/L MP solution into their nostrils for 4 d. One rat in each group was sacrificed for MP nucleic acid detection at the second day after inoculation, and the other rats were given gavage therapy. The rats in blank control group and model group were intragastrically given the same volume of normal saline, the rats in Jiedu-Qingfei group were given 8 mL/kg Jiedu-Qingfei mixture daily for 4 weeks, and the rats in psoitive control group were given dexmethasone sodium phosphate (0.5 mg·kg^-1·d^-1). After the experiment, the rats were killed. The serum and bronchoalveolar lavage fluid (BALF) were collected for detecting the levels of interleukin-12 (IL-12), IL-13 and TNF-α by ELISA. The right lung tissues were used for pathological observation and HE staining, while the left lung tissues were used to detect the expression of NF-κB p50, I-κBα and p38 mitogen-activated protein kinase (p38 MAPK) at mRNA and protein levels. RESULTS: The results of MP nucleic acid detection showed that all the rats except blank control group were MP nucleic acid positive, indicating that the rat model of MP infection was successfully established. On the 1st day of the treatment, the pathological scores of the lung tissues in model group and Jiedu-Qingfei group were significantly higher than those in blank control group (P<0.05). After treatment, the pathological scores of the lung tissues in mo-del group were significantly higher than those in blank control group and Jiedu-Qingfei group. The levels of IL-12 in the serum and BALF in model group were significantly lower than those in blank control group after MP infection (P<0.05), while those after treatment with Jiedu-Qingfei mixture were significantly higher than those in model group (P<0.05). The levels of IL-13 and TNF-α in the serum and BALF of MP-infected rats were increased significantly, while those after treatment with Jiedu-Qingfei mixture were significantly lower than those in model group (P<0.05). The mRNA expression levels of NF-κB p50 and p38 MAPK in model group were increased significantly (P<0.01). After treatment, the mRNA expression levels of NF-κB p50 and p38 MAPK were decreased significantly compared with model group (P<0.01). The mRNA expression level of I-κBα in model group was significantly lower than that in control group. After treatment, the mRNA expression of I-κBα in Jiedu-Qingfei group was significantly higher than that in model group (P<0.05). The protein levels of NF-κB p50 and p38 MAPK in the lung tissues of model group were significantly higher than those of blank control group. After treatment, the protein expression of NF-κB p50 and p38 MAPK was decreased significantly. The protein level of I-κBα in model group was significantly lower than that in blank control group, and after treatment with Jiedu-Qingfei mixture, the protein expression level of I-κBα was increased significantly (P<0.05). CONCLUSION: Jiedu-Qingfei mixture may attenuate lung tissue inflammation caused by MP through NF-κB and p38 MAPK pathways.     

Combined effect of octreotide and Dachaihu decoction on treatment of severe acute pancreatitis

AIM: To investigate the combined effect of octreotide and Dachaihu decoction on the treatment of severe acute pancreatitis(SAP). METHODS: Wistar rats(n=50) were randomly divided into sham group, SAP group, octreotide group, Dachaihu decoction group and combination group. The quantity of ascites was measured. The levels of amylase, alanine aminotransferase and creatinine in the serum were examined. The morphological changes of the pancreatic tissues were observed by HE staining. The activation of NF-κB and IκBα expression were determined by Western blot. The mRNA expression with ICAM-1 and IL-1 was detected by qPCR.RESULTS: Combined treatment with octreotide and Dachaihu decoction effectively reduced the quantity of ascites and the levels of amylase, alanine aminotransferase and creatinine in the serum in SAP rats. Moreover, combined treatment significantly inhibited SAP-induced activation of NF-κB and decrease in IκBα protein expression, accompanied by a decrease in ICAM-1 and IL-1 mRNA expression. CONCLUSION: Combination of octreotide with Dachaihu decoction effectively attenuates SAP by inhibiting NF-κB signaling pathway and ICAM-1 and IL-1 expression.     

α2-adrenoceptor agonist B-HT933 suppresses LPS-induced TNF-α production in neonatal rat cardiomyocytes

AIM: To observe the effect of B-HT933, a selective α₂-adrenoceptor agonist, on lipopolysaccharide(LPS)-induced TNF-α production in neonatal rat cardiomyocytes and to explore the underlying mechanisms.METHODS: The neonatal rat cardiomyocytes were cultured. The localization of α_2A-adrenoceptor in the cardiomyocytes was examined by immunofluorescence staining. The cardiomyocytes were exposed to LPS or/and B-HT933 for different time. The level of TNF-α in the supernatants and the mRNA expression of TNF-α were detected by ELISA and real-time PCR, respectively. In addition, LPS-associated signal molecules in the cardiomyocytes were also examined by Western blotting.RESULTS: Immunofluorescence staining showed that α_2A-adrenoceptors were localized in the cardiomyocytes. LPS stimulated TNF-α production in the cardiomyocytes in a dose and time-dependent manner. B-HT933 pretreatment significantly inhibited the expression of TNF-α at mRNA and protein levels in LPS-treated cardiomyocytes. Furthermore, LPS exposure induced IκBα and p38 phosphorylation in cardiomyocytes and only IκBα phosphorylation was prevented by B-HT933 treatment.CONCLUSION: α_2A-adrenoceptors are present in neonatal rat cardiomyocytes and its agonist B-HT933 inhibits LPS-induced TNF-α production in cardiomyocytes via suppressing IκBα phosphorylation.     

Effects of rhIL-17A on viability and apoptosis of human skin keratinocytes and fibroblasts in vitro

AIM: To investigate the effects of recombinant human interleukin-17A (rhIL-17A) on the viability and apoptosis of human skin keratinocytes and fibroblasts, and to observe the secretion of profibrotic cytokines by fibroblasts. METHODS: Human skin keratinocytes and fibroblasts were treated with different concentrations of rhIL-17A. CCK-8 method was used to test the cell proliferation. The protein expression of nuclear factor-κB/p65 (NF-κB/p65) and IκBα was determined by Western blotting. The cell apoptosis was observed by flow cytometry. The secretion of interleukin-6 and transforming growth factor-β₁ in the culture supernatants of fibroblasts was assayed by ELISA. RESULTS: No difference of the keratinocyte numbers between rhIL-17A treatment groups and control group was observed, while the numbers of fibroblasts were higher in rhIL-17A treatment groups than that in control group (P<0.05). The protein expression of NF-κB/p65 increased in fibroblasts with rhIL-17A treatment, while the expression of IκBα decreased. rhIL-17A had no effect on the apoptosis of both keratinocytes and fibroblasts. The secretion of interleukin-6 and transforming growth factor-β₁ in fibroblasts increased after treated with rhIL-17A. CONCLUSION: rhIL-17A had no effect on the proliferation of keratinocytes. However, it can enhance the proliferation of fibroblasts. This effect may be attributed to the activation of NF-κB in fibroblasts by interleukin-17. It is possible that rhIL-17A causes the cell proliferation and collagen synthesis by stimulating fibroblasts to secrete interleukin-6 and transforming growth factor-β₁.     

Expression of cyclooxygenase-2 in IL-1β-stimulated mesangial cells is medicated by NF-κB/IκB signal pathway

AIM: To investigate the role of NF-κB/IκB signal pathway in the regulation of cyclooxygenase-2 (COX-2) expression in human mesangial cells (HMC). METHODS: The PGE₂ concentration in supernatants of HMC was measured by radioimmunoassay. COX-2 mRNA and protein expression were determined by RT-PCR and Western blot. Electrophoretic mobility shift assay (EMSA) and Western blot were used to detect the activity of NF-κB and degradation of IκB. RESULTS: IL-1β significantly upregulated COX-2 expression and PGE₂ production in HMC. Significant up-regulation of NF-κB activation, nuclear translocation of p65 subunit, and degradation of IκB α and IκB β were observed in IL-1β-induced HMC. CONCLUSION: Expression of COX-2 in IL-1β-induced HMC is mediated by NF-κB/IκB signal pathway.     

Inhibition of HMGB1 expression promotes apoptosis of hemangioma endothelial cells

AIM: To investigate the effect of inhibiting high-mobility group box protein 1 (HMGB1) expression on the viability and apoptosis of hemangioma endothelial cells (HemECs). METHODS: Human HemECs were isolated and cultured, and HMGB1 small interfering RNA (HMGB1-siRNA) was transfected into the cells. The cell viability was detected by CCK-8 assay. The apoptosis and reactive oxygen species (ROS) content were analyzed by flow cytometry. The protein levels of HMGB1, NF-κB p65, p-IκBα, cyclin D1 and survivin were determined by Western blot. RESULTS: The protein expression of HMGB1 in the HemECs transfected with HMGB1-siRNA was significantly lower than that in blank control group (P<0.05). Compared with NC group, the cell viability was decreased significantly in the HemECs transfected with HMGB1-siRNA, the apoptotic rate was significantly increased, the content of ROS increased significantly, and the protein levels of NF-κB p65, p-IκBα, cyclin D1 and survivin were significantly decreased (P<0.05). After exposure to NF-κB signaling pathway inhibitor PDTC, the cell viability was inhibited, the apoptosis was increased, ROS content, and the protein levels of NF-κB p65, p-IκBα, cyclin D1 and survivin were down-regulated significantly, as compared with si-HMGB1 group (P<0.05). CONCLUSION: Inhibition of HMGB1 reduces the viability of HemECs and induces apoptosis by increasing the content of ROS and down-regulating the activity of NF-κB signaling pathway.     

Activation of Akt signal pathway cascades in kidney tissue in murine chronic graft-versus-host disease lupus nephritis and its regulation by prednisone

AIM:To examine whether Akt signal pathway proteins, including Akt, NF-κB and IκBα, are activated in kidney tissue of murine chronic graft-versus-host disease (GvHD) lupus nephritis in vivo, and whether prednisone suppresses activation of them.METHODS:Akt activity and phosphorylated IκBα were detected by Western-blot. Activation of NF-κB was detected by electropheretic mobility shift assay (EMSA). RESULTS:Activity of Akt, NF-κB and phosphorylated IκBα were significantly increased in kidney tissue of murine chronic graft-versus-host disease (GvHD) in 8th week and 12th week after monocell injection, respectively. However, they were no significant elevation in 16th week, when compared with controls. Prednisone treatment significantly prevented the increase in serum anti-dsDNA antibody level, urinary protein excretion and glomerular cell proliferation in GvHD mice, indicating the beneficial effects of prednisone on this model. Prednisone also significantly suppressed the increase in the activities of glomerular Akt, NF-κB and phosphorylated IκBα. CONCLUSION:This study provides the first evidence of marked increase in glomerular Akt-NF-κB signal pathway activities in murine chronic graft-versus-host disease lupus nephritis. The beneficial effect of prednisone on this lupus nephritis model may be partially mediated by the suppression of abnormal Akt- NF-κB activation.     

Effects of amifostine on formation of abdominal aortic aneurysm in mice induced by benzo[a] pyrene

AIM: To study the role of amifostine on the formation of benzo[a]pyrene (BaP)-induced abdominal aortic aneurysm (AAA) in C57BL/6J mice and the underlying mechanism. METHODS: RAW246.7 mononuclear macrophage in vitro were divided into control group, DMSO group, BaP group, low dose (1 μmol/L) amfostine treated group, middle dose (5 μmol/L) amfostine treated group and high dose (25μmol/L) amfostine treated group. The influence of BaP on the expression of matrix metalloproteinase (MMP)-9, MMP-12, TNF-α, NF-κB in the RAW246.7 mononuclear macrophages in vitro was determined by Western blot. Male C57BL/6J mice (8 months old) were divided into control group, model group (AngII+BaP group), low dose (50 mg/kg) amfostine treated group and high dose (100 mg/kg) amfostine treated group. After 6 weeks, the abdominal aorta were isolated. The aortic tissues were subjected to HE and Masson staining. The vascular wall structure, infiltration of macrophage, the expression of MMP-9, MMP-12, TNF-α, NF-κB were evaluated by Western blot and immunochemistry staining. RESULTS: Amifostine attenuated BaP-induced expression of TNF-α, MMP-9, MMP-12, NF-κB in the RAW246.7 mononuclear macrophages (P<0.05). The results of animal experiments showed that the incidence of AAA in high dose amifostine treated group were significantly lower than that in low dose amifostine treated group and model group (P<0.05). Immunohistochemistry staining observation showed that amifostine inhibited the aortic macrophage infiltration more obviously in high amifostine treated group compared with model group and low dose amifostine treated group (P<0.05). Compared with model group and low dose amifostine treated group, the MMP-9, MMP-12, TNF-α and NF-κB expression of abdominal aorta in high amifostine treated group was reduced significantly (P<0.05). CONCLUSION: Amifostine inhibits BaP-induced activation of macrophages, and also prevents the formation of abdominal aortic aneurysm in C57BL/6J mice induced by BaP by inhibition of the NF-κB pathway, macrophage infiltration and the expression of TNF-α and MMPs.     

Protective effect of SIRT1 on rat mesangial cells by decreasing high glucose-induced acetylation of NF-κB p65

AIM: To investigate the effects of silent information regulator 1 (SIRT1) on high glucose-induced acetylation of NF-κB p65 subunit and its protective role in rat mesangial cells. METHODS: Rat mesangial cells were cultured in DMEM supplemented with 10% FBS and were divided into control group, mannitol group, high glucose group, resveratrol group and SIRT1 RNAi group. The cell viability was determined by MTT assay. The mRNA expression of SIRT1, monocyte chemoattratant protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1-1), tumor necrosis factor α (TNF-α), transforming growth factor β1 (TGF-β1) was analyzed by real-time quantitative PCR. The protein expression of SIRT1 and the acetylation of NF-κB p65 subunit were determined by Western blotting. The protein concentrations of MCP-1, VCAM-1, TNF-α, TGF-β1 and malondialdehyde (MDA) were detected by ELISA. RESULTS: The cell viability, superoxide dismutase (SOD) activity, and the expression of SIRT1 at mRNA and protein levels were decreased by high glucose treatment as compared with control group. The acetylation of NF-κB p65 subunit was significantly increased after interfered with high glucose, resulting in the increase in the secretion of MCP-1, VCAM-1, TNF-α and TGF-β1. Resveratrol decreased high glucose-induced acetylation of NF-κB p65 subunit. However, silencing SIRT1 significantly enhanced the acetylation of NF-κB p65 subunit and the expression of MCP-1, VCAM-1, TNF-α and TGF-β1. CONCLUSION: SIRT1 remarkably inhibits the inflammatory reactions by deacetylating NF-κB p65, suggesting that SIRT1 is a possible target for preventing diabetic nephropathy.