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

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

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.

Trichomonas vaginalis is a flagellated lumen-dwelling extracellular protozoan parasite that causes human trichomoniasis via sexual intercourse. Human neutrophils play a crucial role in acute tissue inflammatory responses in T. vaginalis infection. In this study, we investigated the signaling mechanism of neutrophil responses when stimulated with T. vaginalis-derived secretory products (TvSP), which were collected from 1x10(7) live trichomonads. Incubation of human neutrophils isolated from peripheral blood with TvSP induced up-regulation of IL-8 protein secretion. In addition, stimulation with TvSP induced phosphorylation of NF-kappaB and CREB in neutrophils. Moreover, TvSP-induced IL-8 production was also significantly inhibited by pretreatment of neutrophils with ikappaB inhibitor or CREB inhibitor. These results suggest that transcription factors NF-kappaB and CREB are involved in IL-8 production in human neutrophils induced by stimulation with T. vaginalis infection.
Cyclic AMP Response Element-Binding Protein/*metabolism ; Human Experimentation ; Humans ; Interleukin-8/*metabolism ; Male ; NF-kappa B/*metabolism ; Neutrophils/*immunology ; Phosphorylation ; Trichomonas vaginalis/*immunology

BACKGROUND/AIMS: Nuclear factor-kappa B p65 (NF-kappa B p65), nuclear factor-kappa B1 p50 (NF-kappa B p50) have been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. Recently, p38 mitogen-activated protein kinase (MAPK)/ NF-kappa B/ cyclin D1 signaling pathway has been shown to play an important part in the pathogenesis of human cancers. This study was designed to investigate the expression of NF-kappa B p65, NF-kappa B p50, p38 MAPK alpha, and cyclin D1 proteins in premalignant lesions of colon and colorectal adenocarcinoma. METHODS: Paraffin sections of 20 normal mucosa, 20 low-grade tubular adenoma, 20 high-grade tubular adenoma and 64 adenocarcinoma tissues were analysed immunohistochemically for the expression of NF-kappa B p65, NF-kappa B p50, p38 MAPK alpha, and cyclin D1 proteins. RESULTS: The expression of NF-kappa B p65, NF-kappa B p50, and p38 MAPK alpha proteins were significantly higher in adenocarcinoma tissue in comparison with that in normal mucosa, low-grade tubular adenoma, and high-grade tubular adenoma tissues. Expression of NF-kappa B p50 was more frequent in poorly differentiated histologic grade, presence of nodal metastasis, and advanced stage. Expression of p38 MAPK alpha protein was higher in advanced tumor stage, presence of nodal metastasis and advanced stage. Synchronous expression of NF-kappa B p65, NF-kappa B p50, p38 MAPK alpha, and cyclin D1 proteins were significantly higher in adenocarcinoma tissue. CONCULSIONS: With the increased expression of NF-kappa B p65, NF-kappa B p50, and p38 MAPK alpha proteins, p38 MAPK/ NF-kappa B/ cyclin D1 signaling pathway may play a role in the pathogenesis of colorectal carcinoma.
Adenocarcinoma/enzymology/*metabolism/pathology ; Colorectal Neoplasms/enzymology/*metabolism/pathology ; Cyclin D1/immunology/*metabolism ; Data Interpretation, Statistical ; Female ; Humans ; Immunohistochemistry ; Intestinal Mucosa/metabolism ; Male ; Middle Aged ; NF-kappa B/immunology/*metabolism ; NF-kappa B p50 Subunit/immunology/metabolism ; Neoplasm Staging ; Precancerous Conditions/enzymology/*metabolism ; Transcription Factor RelA/immunology/metabolism ; p38 Mitogen-Activated Protein Kinases/*metabolism

<b>OBJECTIVEb>To explore the influence of ischemia/reperfusion (anoxia/reoxygenation) on immunofunction of endothelial cells (ECs) and effect of intervention with Yisheng injection (YSI, a pure natural medicine) on it.

<b>METHODSb>Model of ECs induced by anoxia/reoxygenation was established to mimic ECs ischemia/reperfusion injury in vivo with human umbilical vein endothelial cell line ECV304. Then YSI was used to intervene the anoxia/reoxygenation process. Nuclear transcriptional factor-kappa B (NF-kappa B) was exhibited by fluorescent staining, HLA-ABC, HLA-DR, CD86 and CD54 were detected by flow cytometry. Mixed endothelial cell-lymphocyte reaction (MELR) was conducted to examine the proliferation of lymphocyte, production of IL-2 and percentage of apoptotic lymphocyte.

<b>RESULTSb>Anoxia/reoxygenation made the ECV304 cell became round, shrunk and abscised, with increased plasma NF-kappa B, and changed from positive cytoplasm to positive nucleus. HLA-ABC, HLA-DR and CD86 on surface of cells increased but CD54 showed unchanged. MELR showed the incorporation of 3H-TdR and production of IL-2 increased significantly and the percentage of apoptotic lymphocyte decreased. After YSI intervention, the ECV304 cell shaped recovered, NF-kappa B expression didn't down-regulated, but the percentage of positive cells decreased, changed to positive dominant. Besides, reversal changes were shown in other parameters.

<b>CONCLUSIONb>Anoxia/reoxygenation influences some important immune related molecules in ECV304 cells, YSI could antagonizing these influences to maintain the immune function of endothelial cells in a relative normal manner.

Cell Hypoxia ; Cell Line ; Drugs, Chinese Herbal ; pharmacology ; Endothelium, Vascular ; cytology ; immunology ; Humans ; NF-kappa B ; metabolism ; Oxygen ; pharmacology ; Phytotherapy ; Reperfusion Injury ; immunology ; Umbilical Veins ; cytology

<b>OBJECTIVEb>To explore the activity of nuclear factor kappa B (NF-kappaB) in peripheral blood lymphocytes (PBL) of patients with hepatitis B.

<b>METHODSb>The PBL of patients with different types of hepatitis B and healthy individuals were isolated and then the nuclear extract was prepared. Assessment of NF-kappaB DNA binding activity was performed by electrophoretic mobility shift assay (EMSA) using digoxin labeled double-stranded oligonucleotide containing kappa B consensus sequence.

<b>RESULTSb>Densitometric scanning of the EMSA bands showed that the mean optical densities (A) from the groups of normal control, acute hepatitis B, chronic hepatitis B and chronic severe hepatitis B were 20.18+/-2.16, 27.75+/-4.11, 13.90+/-3.20 and 8.02+/-2.65 respectively. Analysis of variance showed the F value was 26.112 and the difference among the groups was significant. The difference between two groups with Dunnett T3 analysis showed there are statistically difference between the groups of the normal group and the chronic severe hepatitis B group, the acute hepatitis B group and the chronic hepatitis B group, and the acute hepatitis B group and the chronic severe hepatitis B.

<b>CONCLUSIONb>The activity of NF-kappaB in PBL of patients with hepatitis B is related with the different outcomes of hepatitis B virus (HBV) infection. Decreased activity of NF-kappaB may be an important cause for the dysfunction of PBL in chronic HBV-infected patients.

Adult ; Electrophoretic Mobility Shift Assay ; Female ; Hepatitis B, Chronic ; blood ; immunology ; Humans ; Lymphocytes ; metabolism ; Male ; Middle Aged ; NF-kappa B ; blood

<b>OBJECTIVEb>To investigate the regulation of Toll-like receptors (TLRs) on immune suppressive cytokines in situ colon cancer cells.

<b>METHODSb>The mRNA and protein expression spectrum of TLRs in HT-29 cells were determined by RT-PCR and Western blot respectively. The cytokines and chemokines levels of supernant of HT-29 stimulated by lipoplysaccharide(LPS) were detected with ELISA.

<b>RESULTSb>TLR1-9 were expressed in HT-29 cells on mRNA level. After LPS stimulation, TLR4 mRNA and protein expressions were up-regulated in HT-29 cells, and TGF-beta, VEGF, IL-8, CCL20 and IL-6 levels increased significantly(all P<0.01). Except IL-6, up-regulation of the other cytokines was not suppressed by NF-kappa B inhibitor.

<b>CONCLUSIONb>TLRs expressed on colon cancer cells may elevate the immune suppressive cytokines and chemokines, which promote the immune escape of cancer cells.

Chemokine CCL20 ; metabolism ; Colonic Neoplasms ; immunology ; metabolism ; Cytokines ; immunology ; HT29 Cells ; Humans ; Interleukin-6 ; metabolism ; NF-kappa B ; metabolism ; RNA, Messenger ; genetics ; Signal Transduction ; Toll-Like Receptor 4 ; immunology ; metabolism ; Transforming Growth Factor beta ; metabolism ; Up-Regulation

Animals ; Male ; NF-kappa B ; metabolism ; Otitis Media with Effusion ; immunology ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Th1 Cells ; cytology ; Th2 Cells ; cytology