Nuclear factor κB (NF-κB), including RelA, RelB, c-Rel, NF-κB1, and NF-κB2, plays a crucial role in immune response, inflammatory reaction, tumorigenesis, and development of peripheral lymphoid organs and lymphocytes. There are two NF-κB activation pathways: canonical pathway (classical pathway) and noncanonical pathway (alternative pathway). Previous studies focused on the effects of the canonical NF-κB pathway (mainly p50-RelA) in hematological malignancies. Recently, the noncanonical NF-κB pathway (mainly p52-RelB) is gradually taken importance in pathogenesis of hematological malignancies. Understanding the relations of the noncanonical pathway with hematological malignancies would provide a new therapeutic approach for these diseases. This review focuses on the noncanonical NF-κB signaling transduction pathway and its relation to hematologic malignancies.
Hematologic Neoplasms ; metabolism ; Humans ; NF-kappa B ; metabolism ; NF-kappa B p50 Subunit ; metabolism ; NF-kappa B p52 Subunit ; metabolism ; Signal Transduction

The nuclear factor kappa B(NF-kappaB) plays a crucial role in inflammatory, immune response, embryo development, cell proliferation and apoptosis, cell cycle control as well as tumorgenesis. In recent years, a variety of investigations have demonstrated that NF-kappaB was closely associated with the pathogenesis of hematological malignancies such as leukemia, lymphoma and multiple myeloma. Nowadays, increasingly attention has been paid to the studies on the activation and its mechanism of NF-kappaB in the hematogenic malignancies. So that, in this article, progress on these aspects is reviewed.
Hematologic Neoplasms ; metabolism ; pathology ; Humans ; NF-kappa B ; metabolism

Colon cancer is the 3rd common malignancy and 4th common cause of cancer death in Korea. Recent studies have shown that abnormal inflammatory response plays a critical role in colon carcinogenesis. A striking example of connection between inflammation and cancer is NF-kappaB, in which key regulator of inflammation and immune response is associated with target for colon cancer treatment. Constitutive NF-kappaB expression in colon cancer is 40-80% in vivo as well as in vitro, and the inactivation of IKKbeta subunit can reduce tumor multiplicity. The possible mechanisms by which NF-kappaB can contribute to colon carcinogenesis include the activator of antiapoptotic gene expression, enhanced cell survival and proliferation, regulation of angiogenesis and promotion of metastasis of cancer cells. Recent insights into the role of NF-kappaB involved in colon cancer development as well as their relevance as therapeutic targets are herein discussed.
Colonic Neoplasms/*etiology/metabolism ; Humans ; I-kappa B Kinase/metabolism/physiology ; Inflammation ; NF-kappa B/metabolism/*physiology

In recent years, it is found that the classical IKKα and IKKβ pathway were closely relates with hematological tumors, except the classical pathogenesis, moreover the classical IKKβ pathway is deeply studied. The studies indicated that the IKKβis activated to phosphorylate the NF-κB through multiple cascades under the effect of extracellular IL-6, TNF-α and other stimulating factors. At the cellular level, the classical IKKβcan promote the tumor cell survival and proliferation, reduce the cell apoptosis, and promote the angiogenesis and cell transfer. Although the classical IKKα plays a role in regulating IKKβ activity, but its role in non-classical pathway is more prominent. This review briefly summarizes the latest advance of researches on the pathogenesis of hematological malignancies in term of IKKα and IKKβpathway, so as to provide the theoretic basis for deeply understanding and studying the pathogenesis of hematologic tumors. At present, blocking the classical IKKα and IKKβ pathway has become a new target for treatment of hematological tumors, moreover, some specific inhibitor for IKKα and IKKβpathway have been developed, for example, LY2409881, BMS 345541 and so on. Most of these drugs are in clinical trials and display some good anti-tumor effects.
Cell Survival ; Hematologic Neoplasms ; Humans ; I-kappa B Kinase/metabolism* ; NF-kappa B/metabolism* ; Signal Transduction ; Tumor Necrosis Factor-alpha

Cholestasis ; metabolism ; Humans ; NF-kappa B ; metabolism ; Pneumonia ; metabolism ; Toll-Like Receptor 4 ; metabolism

Carcinoma, Hepatocellular ; metabolism ; pathology ; Hepatocytes ; metabolism ; pathology ; Humans ; Liver Neoplasms ; metabolism ; pathology ; NF-kappa B ; metabolism

Objective:b> To study the mechanisms of cold exposure mediated ileum mechanical barrier injury in mice. Methods:b> Twenty mice were randomly divided into the control and cold exposure groups. Both the control and cold exposure groups were placed in the climate room with (24±2)℃ and 40% humidity. The mice in the cold exposure group were moved to the climate room at (4±2)℃ every day for 3 hours for three consecutive weeks. Three weeks later, the ileum tissues of mice were collected. Changes in ileum tissue structure were observed by hematoxylin-eosin staining and Masson staining. The related protein expression levels of the tight junction, inflammatory cytokines, and the NF-κB pathway were detected by Western blot. Results:b> Compared with the control group, the circular muscle layer of the ileum in cold exposed mice became thin, a large number of inflammatory cells infiltrated, the length of villi became short, the depth of recess was increased, and tissue fibrosis appeared. The expression levels of ideal tight junction-associated proteins in cold exposed mice were decreased significantly (P＜0.05), while the protein expression levels of IL-1β, IL-6 and phosphorescent p65 were increased significantly (P＜0.05). Conclusion:b> Cold exposure can damage the tight junction of the mouse ileum, destroy the integrity of the mechanical barrier and activate the NF-κB signaling pathway to promote the occurrence of the inflammatory response.
Animals ; Cytokines/metabolism* ; Ileum/metabolism* ; Intestinal Mucosa ; Mice ; NF-kappa B/metabolism* ; Tight Junctions/metabolism*

This study was aimed to explore the expression of survivin and NF-kappaB in the peripheral T-cell lymphoma and its significance. Immunohistochemistry method was used to detect the expressions of survivin and NF-kappaB in 26 cases of lymphosarcoma. 30 cases of benign reactive lymphohistiocytosis were selected as control tor analysis. The results showed that the expression of survivin in 21 patients with lymphoma was positive, the positive rate reached to 80.8%; the expression of NF-kappaB in 17 cases was positive, the positive rate reached to 65.4%. Compared with the control group, the difference was statistically significant (p < 0.01). In the experimental group, the expression level of survivin was positively correlated with the positive rate of NF-kappaB. It is concluded that survivin and NF-kappaB widely expressed in lymphoma cells and they play an important role in enhancing proliferation and inhibiting apoptosis of tumor cells.
Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Lymphoma, T-Cell, Peripheral ; metabolism ; pathology ; NF-kappa B ; metabolism

Inflammatory bowel disease refers to chronic inflammatory disorders that affect the gastrointestinal tract. Ubiquitination is an important protein post-translational modification. In recent years, the research of ubiquitination-deubiquitination system in the development of inflammatory bowel disease has become a hot spot. Up to now, the E3 ubiquitin ligases such as ring finger protein 183 (RNF183), RNF20, Itch and A20 were well studied in inflammatory bowel disease. RNF183 promotes the activation of the NF-κB pathway by increasing the ubiquitination and degradation of IκBα; RNF20 drives histone H2B monoubiquitylation, downregulates a panel of inflammation-associated genes; Itch inhibits IL-17-mediated colon inflammation by retinoid acid related orphan receptor γt ubiquitination; A20 has ubiquitinating-deubiquitinating activity to regulates colon inflammation. This article reviews the role and regulatory mechanism of RNF183, RNF20, Itch and A20 in the pathogenesis of inflammatory bowel disease.
Histones ; metabolism ; Humans ; Inflammatory Bowel Diseases ; physiopathology ; NF-kappa B ; metabolism ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitination

<b>OBJECTIVEb>To investigate the cytotoxicity of bromoxynil on SH-SY5Y cells and its effect on the expression of nuclear factor-kappa B (NF-&kappa;B) and I kappa B alpha (I&kappa;Bα) in SH-SY5Y cells.

<b>METHODSb>SH-SY5Y cells were exposed to bromoxynil (10, 50, or 100 µmol/L) for 24 and 48 h, and other SH-SY5Y cells, which were used as a control, were exposed only to dimethyl sulfoxide. After 24 and 48 h of exposure, the morphological changes of these cells were observed under an inverted microscope, and the cytotoxicity of bromoxynil was measured by MTT assay. The cellular proliferation was examined by cell counting after 12, 24, 48, 72, and 96 h of exposure. After 24 h of exposure, the expression of NF-&kappa;B was evaluated by Western blot and immunocytochemistry, and the expression of I&kappa;Bα was evaluated by Western blot.

<b>RESULTSb>The cellular proliferation inhibition rates (CPIRs) of 50 and 100 µmol/L groups were significantly higher than that of the control group after 24 and 48 h of exposure (P < 0.05); the CPIR was significantly higher after 48 h than after 24 h in the two groups (P < 0.05). The growth curve revealed that these groups began to show differences in cell count at the 24th of exposure and that the differences were even more marked as the exposure went on (F = 17.15, P < 0.05). The control group had a significantly increased cell count at the 48th, 72nd, and 96th h of exposure (P < 0.05); the 10 and 50 µmol/L groups had a significantly increased cell count at the 72nd and 96th h of exposure (P < 0.05); the 100 µmol/L group showed no significant change in cell count during 96h of exposure. The 50 and 100 µmol/L groups hada significantly longer cell doubling time than the control group (P < 0.05). The immunocytochemistry showed that as the dose of bromoxynil increased, the brownish yellow particles in the cytoplasm and nuclei became darker, the expression of NF-&kappa;B was upregulated, and the nuclear translocation of NF-&kappa;B was increased. The Western blot showed that the 100 µmol/L group had significantly higher expression of NF-&kappa;B in the nuclei than the control group (P < 0.05) and that the 50 and 100 µmol/L groups had significantly lower expression of I&kappa;Bα in total proteins than the control group (P < 0.05).

<b>CONCLUSIONb>Bromoxynil can inhibit the proliferation of SH-SY5Y cells under this experimental condition, which may be related to activation of NF-&kappa;B.

Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; I-kappa B Proteins ; metabolism ; NF-KappaB Inhibitor alpha ; NF-kappa B ; metabolism ; Nitriles ; toxicity