Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint swelling and progressive destruction of cartilage and bone. Current RA treatments are largely empirical in origin and their precise mechanism of action is uncertain. Increasing evidence shows that chronic inflammatory diseases such as RA are caused by prolonged production of proinflammatory cytokines including tumor necrosis factor (TNF) and interleukin 1 (IL-1). The nuclear factor kappaB (NF-kappaB) plays an essential role in transcriptional activation of TNF and IL-1. NF-kappaB is induced by many stimuli including TNF and IL-1, forming a positive regulatory cycle that may amplify and maintain RA disease process. NF-kappaB and enzymes involved in its activation can be a target for anti-inflammatory treatment. Aspirin and sodium salicylate inhibit activation of NF-KB by blocking IkappaB kinase, a key enzyme in NF-kappaB activation. Glucocorticoids suppress expression of inflammatory genes by binding glucocorticoid receptor with NF-kappaB, and increasing expression of inhibitory protein of NF-kappaB, IkappaBalpha. Sulfasalazine and gold compounds also inhibit NF-kappaB activation. Continuing advances in our understanding of action mechanism of antirheumatic agents will benefit the future development of RA regimens with greater efficacy and less toxicity.
Animal ; Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/therapy* ; Arthritis, Rheumatoid/metabolism ; Arthritis, Rheumatoid/immunology ; Cytokines/immunology ; Cytokines/genetics ; Gene Expression Regulation ; Human ; Macrophages/immunology ; NF-kappa B/metabolism* ; NF-kappa B/immunology ; NF-kappa B/biosynthesis ; Tumor Necrosis Factor/genetics

NF-kappaB is a kind of important nuclear factors which are relative to lots of cellular activities such as activation of immunocyte, development of T and B lymphocyte, stress reaction, cell apoptosis and so on. NF-kappaB exists in almost all types of cytoplasm in the unreactive form of heterodimer or homodimer. Recent studies have shown that there is close relationship between NF-kappaB and pathogenesis of hematopoietic malignancies such as leukemia, lymphoma and multiple myeloma. In this review, the advances of studies on the role of NF-kappaB in hematopoietic malignancies were summarized, including subunits of NF-kappaB and its activity, activity of NF-kappaB and its effect on apoptosis, activity of NF-kappaB in AML cells and its mechanism, activity of NF-kappaB in ATL cells and its mechanism, activity of NF-kappaB in lymphoma and its mechanism, activity of NF-kappaB in multiple myeloma cells and its mechanism, application of NF-kappaB suppression in hematopoietic malignancies and so on.
Apoptosis ; physiology ; Hematologic Neoplasms ; etiology ; immunology ; pathology ; Humans ; NF-kappa B ; immunology ; metabolism

Many Chinese drugs (CHD) have showed their significant effects of integral immune-regulation, and lots of researches have conducted in recent years for exploring their mechanism from different levels, like cytological, molecular and genetic levels. In this paper, the relation between immune-regulation of CHD and Toll-like receptors/nuclear factor-kappaB (TLRs/NF-kappaB) signaling pathway was introduced in brief based upon the achievements of previous researches. It was pointed out that the two are closely related, to explore mechanism of CHD in this way is meaningful not only for further deepening the theoretical understanding of CHD's pharmacological immunoregulation, but also be practically facilitate for enhancing therapeutic efficacy of CHD and developing new CHD.
Adjuvants, Immunologic ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; NF-kappa B ; immunology ; Signal Transduction ; drug effects ; Toll-Like Receptors ; immunology

Staphylococcus aureus (S. aureus) is an important human pathogen which can cause a chronic condition with a high relapse rate despite the aggressive antimicrobial treatment. Recent studies showed that intracellular pattern recognition receptors (including NOD) in response to bacteria or bacterial products play a proinflammatory role by activating nuclear transcription factor-κB (NF-κB). But how NOD2 mediates the proinflammatory response to S. aureus in mast cells (MCs) is unclear. So, in this study, we attempted to examine the role of NOD2 in inflammatory responses of MCs to S. aureus. P815 cells (a mouse mast cell line) were cultured. Real-time PCR was used to detect the NOD2 mRNA expression in P815 cells during S. aureus infection. The siRNA against NOD2 gene was synthesized and transfected into S. aureus-infected P815 cells. By using the methods of ELISA and flow cytometry, the effects of NOD2 gene silencing on cell phagocytosis, cytokine secretion, NF-κB activation and cell apoptosis of the S. aureus-infected P815 cells were examined. It was found that S. aureus infection could increase the expression of NOD2 mRNA in P815 cells. NOD2 gene interference in P815 cells reduced the number of S. aureus engulfed by P815 cells, the level of cytokines and the activation of NF-κB. In addition, S. aureus could induce the apoptosis of P815 cells, but NOD2 gene silencing did not affect the cell apoptosis rate. Our data suggested that NOD2 plays a key role in pathogen recognition, signal transduction, and NF-κB activation in the inflammatory responses of MCs infected by S. aureus.
Animals ; Cell Line ; Cytokines ; immunology ; Inflammation Mediators ; immunology ; Mast Cells ; immunology ; microbiology ; Mice ; NF-kappa B ; immunology ; Nod2 Signaling Adaptor Protein ; immunology ; Staphylococcus aureus ; physiology

This study examined the effects of Bangdeyun on the expressions of nuclear factor-kappaB (NF-kappaB), interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) in the endometrium of mice with embryo implantation dysfunction (EID) during the implantation time (namely on pregnancy day 5, 6, 7 and 8) and explored the local immune regulatory effects of Bangdeyun. The gestational mice were randomly divided into normal group, model group and Bangdeyun-treated group. EID models of mice were established by using indomethacin. The endometrial expression of NF-kappaB was detected by immunohistochemistry and Western blotting. IFN-gamma and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that in the normal group, NF-kappaB and IFN-gamma were weakly expressed and IL-10 was strongly expressed in the endometrium during the whole implantation period. In the model group, the expressions of NF-kappaB and IFN-gamma were increased on pregnancy day 5, 6 and 7, and IL-10 expression decreased during the whole implantation time when compared with those in the normal group (P<0.01 for all). In the Bangdeyun-treated group, little amount of NF-kappaB and IFN-gamma was expressed and IL-10 expression was strong, much the way they were expressed in the normal group (P>0.05). The expressions of NF-kappaB and IFN-gamma were much lower in the Bangdeyun-treated group than those in the model group on pregnancy day 5, 6 and 7 (P<0.01 for all), while the expression of IL-10 was much higher than in the model group during the whole implantation time (P<0.01). It was suggested Bangderun may favor a shift from Th1- to Th2-type immune response, therefore inhibiting the maternal immune rejection, inducing the immune tolerance and improving the fetal implantation.
Drugs, Chinese Herbal/*pharmacology ; Embryo Implantation, Delayed/*drug effects ; Embryo Implantation, Delayed/immunology ; Endometrium/*immunology ; Endometrium/metabolism ; Interferon-gamma/genetics ; Interferon-gamma/metabolism ; Interleukin-10/genetics ; Interleukin-10/metabolism ; NF-kappa B/genetics ; NF-kappa B/metabolism

Burns ; immunology ; Chemokine CCL2 ; immunology ; Humans ; Infection ; immunology ; Macrophages ; immunology ; Membrane Glycoproteins ; immunology ; NF-kappa B ; immunology ; Receptors, Cell Surface ; immunology ; T-Lymphocytes ; immunology ; Toll-Like Receptors ; Transcription Factor AP-1 ; immunology

Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and deveolpment of pancreatitis. A hallmark of the inflammatory response is the induction of cytokine gene expression, which may be regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF-KB). Present study aims to investigate whether neutrophils primed by 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) affect the productions of H2O2 and lipid peroxide (LPO), NF-kappaB activation and cytokine production in pancreatic acinar cells, and whether these alterations were inhibited by N-acetylcysteine (NAC) and superoxide dismutase (SOD). ROS generation in neutrophils increased by PMA, which was inhibited by NAC and SOD. The productions of H2O2, LPO and TNF-alpha were increased with the amounts of PMA-primed neutrophils added to acinar cells while the productions of H2O2, LPO and cytokines increased with time. PMA-primed neutrophils resulted in the activation of two species of NF-kappaB dimers (a p50/p65 heterodimer and a p50 homodimer). Both NAC and SOD inhibited neutrophil-induced alterations in acinar cells. In conclusion, ROS, generated by neutrophils, activates NF-kappaB, resulting in upregulation of inflammatory cytokines in acinar cells. Antioxidants such as NAC might be clinically useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-KB and decreasing cytokine production.
Acute Disease ; Chronic Disease ; Cytokines/immunology* ; Human ; NF-kappa B/metabolism* ; Pancreas/metabolism* ; Pancreas/immunology* ; Pancreas/cytology ; Pancreatitis/metabolism ; Pancreatitis/immunology ; Support, U.S. Gov't, Non-P.H.S.

To study the anti-inflammatory activity of glycyrrhizin acid, ligustrazine and puerarin. In the study, the liquichip-based high-throughput synchronous detection technique for 23 inflammatory factors, uniform design, comprehensive weight method were adopted to study the effect of different combined administration of glycyrrhizin acid, ligustrazine and puerarin in inhibiting the expression of lipopolysaccharide (LPS)-induced RAW264. 7 cells and multiple inflammatory cytokines. In the study, the uniform design table U₉ (9³) was adopted to design doses of glycyrrhizin acid, ligustrazine and puerarin. The liquichip technique was used to detect the effect of different combined administration of glycyrrhizin acid, ligustrazine and puerarin on the 23 cytokines expressed in LPS-induced mouse macrophage RAW264. 7 inflammation model. The traditional Chinese medicine component optimization software and the improved least angle regression algorithm were used to analyze the dose-effect relationship among the three components and the cytokine inhibition rate and produce the regression equation. The comprehensive weight method was applied to get the optimal dose ratio of glycyrrhizic acid, ligustrazine and puerarin with highest efficacy of 25:2:13 and verify the optimal dose ratio. The verification results were consistent with the prediction trend, indicating the accuracy of the mathematical model for predicting the experiment. The experimental results showed the multi-target and multi-level efficacies of glycyrrhizic acid, ligustrazine and puerarin and the high anti-inflammatory activity of their combined administration, which provides powerful basis for subsequent drug development.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Cytokines ; Glycyrrhizic Acid ; pharmacology ; Isoflavones ; pharmacology ; Lipopolysaccharides ; immunology ; Macrophages ; drug effects ; immunology ; Mice ; NF-kappa B ; genetics ; immunology ; Pyrazines ; pharmacology ; RAW 264.7 Cells

To investigate the effects of DENV infection on the expression of Vascular endothelial growth factor (VEGF) in monocytes, and to explore which innate immune signaling pathway is responsible for VEGF induction. Real-time PCR was used to determine the expression levels of VEGF in DENV-infected THP-1. We found that different serotype viruses (DENV1, DENV2, DENV3) induced the VEGF expression. Moreover, VEGF expression was significantly increased in human primary monocytes infected with DENV 2. In addition, VEGF induction by DENV2 was significantly impaired by knockdown of TLR3 and interferon-beta promoter stimulator 1 (IPS-1), or by inhibition of ERK, JNK or NF-kappaB. These results demonstrated that DENV induced VEGF expression in monocytes, and the activation of TLR3, IPS-1 signal pathways were required for DENV2-triggered VEGF induction, suggesting that VEGF might be a promising therapeutic target for DHF.
Dengue ; genetics ; immunology ; virology ; Dengue Virus ; classification ; genetics ; physiology ; Humans ; MAP Kinase Signaling System ; Monocytes ; NF-kappa B ; genetics ; immunology ; Up-Regulation ; Vascular Endothelial Growth Factor A ; genetics ; immunology

<b>OBJECTIVEb>To observe the effects of ox-LDL on monocyte-derived dendritic cells.

<b>METHODSb>DCs were derived from healthy donors and divided into four groups according to the method of stimulation. The cells of blank group, negative group, experimental group and positive group which were treated with PBS, LDL, ox-LDL, TNF-alpha, individually. ox-LDL was added during the late stage of monocyte differentiation. Flow cytometry was used to analyze the cell surface markers and the endocytoses of DCs. (3)H-TdR incorporation was used to measure the proliferation of syngeneic and allogeneic T cells. ELISA assay was used to measure IL-12, MCP-1and MIP1 in cultured medium. Western blot analysis was used to evaluate the content of IkappaBalpha and NF-kappaB of DCs.

<b>RESULTSb>Addition of ox-LDL during the late stage of monocytes differentiation can upregulate the cell surface markers including CD40 (22.3% vs. 45.6%) and CD86 (25.9% vs. 82.4%), increase the secretion of IL-12 (31.43 pg/ml vs. 126.73 pg/ml) and MCP-1 (59.6 ng/ml vs. 116.3 ng/ml), reduce DCs uptake capacity (46.8% vs. 10.7%), enhance allogeneic T cells proliferation (SI: 4.5 vs. 5.7), promote IkappaBalpha degradation and upregulate the expression of NF-kappaB in DCs.

<b>CONCLUSIONb>ox-LDL can promote the maturation of PBMCs-derived DCs by promoting IkappaBalpha degradation.

Cell Differentiation ; Cells, Cultured ; Dendritic Cells ; cytology ; immunology ; metabolism ; Flow Cytometry ; Humans ; I-kappa B Proteins ; metabolism ; Lipoproteins, LDL ; pharmacology ; Monocytes ; cytology ; drug effects ; NF-KappaB Inhibitor alpha ; NF-kappa B ; metabolism