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

Humans ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; metabolism ; NF-kappa B p50 Subunit ; metabolism ; Transcription Factor RelA ; metabolism

OBJECTIVE: To study the expression and activation of p50 subunit of nuclear factor-kappa B(NF-kappaB) in mucosa of seasonal allergic rhinitis. METHOD: The expression of p50 subunit of NF-kappaB in the mucosa from 16 patients (6 patients with symptom, 10 patients without symptom)and 10 normal subjects were detected by immunohistochemistry. The activation of DNA-binding proteins which was labeled with 32P-radiolabeled oligonucleotide probe for NF-kappaB was detected with electrophoretic mobility shift assays(EMSA) in mucosa. RESULT: The expression of p50 subunit of NF-kappaB was observed in the nasal mucosa of SAR and normal samples. The expression of p50 subunit of NF-kappaB was positive in the cytoplasm and some nuclei of the mucosal epithelia, inflammatory cells, glandular epithelia, and vascular endothelia in nasal mucosa. The Rate of nucleus positive staining of p50 was (41.83 +/- 4.43)% and(37.19 +/- 3.93)% in SAR with symptom and SAR without symptom patients,respectively. There was no significant difference (P > 0.05). The Rate of nucleus positive staining of p50 in nasal mucosa of normal samples was (8.89 +/- 1.32)%. The difference of p50 subunit of NF-kappaB expression between SAR group and normal group was statistically significant (P < 0.01). The DNA-binding proteins activity of samples from patients with seasonal allergic rhinitis was stronger than that in normal subjects (P < 0.05). CONCLUSION p50 subunit of NF-kappaB was activated in healthy nasal mucosa to some extent. The expression and DNA-binding proteins activity of p50 subunit of NF-kappaB was enhanced in seasonal allergic rhinitis. It indicated that p50 subunit of NF-kappaB may be involved in nasal mucosa physiological function and may have an important role in maintaining the chronic inflammation in seasonal allergic rhinitis.
Case-Control Studies ; Humans ; NF-kappa B p50 Subunit ; genetics ; metabolism ; Nasal Mucosa ; metabolism ; Rhinitis, Allergic, Seasonal ; metabolism

<b>OBJECTIVEb>To investigate the effects of burn sera on the nuclear translocation of endothelial NF-kappaB heterodimers p50/p65 and on the degradation of inhibiting kappaB (IkappaBalpha), in order to explore the role of burn sera on activation of the endothelium.

<b>METHODSb>Cultured human umbilical vein endothelial cells (HUVECs) (ECV-304 strain) were employed as the target cells. The cells were stimulated by sera from healthy volunteers and from burn patients and burn sera together with PDTC (pyrrolidine dithiocarbarnate). The normal cultured cells were taken as the control. The nuclear translocation of endothelial p50/p65 at 30, 60, 120 and 480 mins after the stimulation was observed with laser confocal microscopy, and the endothelial IkappaBalpha protein degradation at 30, 60, 90 and 120 mins after the stimulation was determined by Western blotting.

<b>RESULTSb>When compared to that in control group, the nuclear translocation of p50/p65 took place 30 mins after the endothelial cells were stimulated by burn sera, and it reached the summit at 30 - 60 mins, but recovered to pre-stimulation state at 2hrs. In addition, IkBalpha degradation occurred 30 mins after the cells were stimulated by burn sera (P < 0.01) and peaking at 45 - 60 mins after the stimulation and recovered at 2hrs after the stimulation. The nuclear translocation of endothelial p50/p65 and IkBalpha degradation at 30 and 60 mins after the stimulation by burn sera could be effectively inhibited by PDTC.

<b>CONCLUSIONb>Burn sera might induce the nuclear translocation of endothelial NF-kappaB p50/p65 and IkappaBalpha degradation and activate NF-kappaB, which ultimately lead to the secretion of cytokines from the endothelium.

Active Transport, Cell Nucleus ; Adolescent ; Adult ; Burns ; blood ; Female ; Humans ; I-kappa B Proteins ; analysis ; Male ; Middle Aged ; NF-KappaB Inhibitor alpha ; NF-kappa B ; metabolism ; NF-kappa B p50 Subunit ; Transcription Factor RelA

<b>OBJECTIVEb>To investigate the function of alternative NF-&kappa;B activity in B-cell chronic lymphocytic leukemia cells (B-CLL).

<b>METHODSb>The mRNA expression of individual NF-&kappa;B subunits in CD5⁺CD19⁺ cells (CLL B-cells) from bone marrow (BM) of 56 patients with B-CLL was analyzed by quantitative RT-PCR. An ELISA-based NF-&kappa;B family transcription factor activity assay was performed to quantify the &kappa;B DNA-binding activity in nuclear extracts from CLL B-cells. Cell death of CLL-B cells was determined by PI staining, RelA and RelB expression at protein level of CLL B-cells by Western blot analyses.

<b>RESULTSb>The expression levels of RelA, p50, RelB and p52 mRNA in CLL B-cells were all higher than that of normal B cells with statistical significance (P<0.05). RelA was activated in almost all the patients detected while RelB activity was induced in part of samples. The average RelA activity in CLL B-cells was increased compared to that in normal B cells while the average RelB activity was similar to that of normal B cells. When cultured in vitro for 24, 48 and 72 hours, the frequencies of cell death of CLL B-cells from RelA⁺/RelB⁻ group were(35.54±4.43)%,(50.92±8.44)%, and(49.24±8.16)%, respectively; that of the RelA⁺/RelB⁺ group were (20.65±2.37)%, (18.17±1.36)%, and (26.55±4.08)%, respectively. When the cells from RelA+/RelB⁻ group were co-cultured with bone marrow stromal cells (hBMSCs), the frequencies of cell death of CLL B-cells were decreased compared to that of the cells cultured alone, while the frequencies of cell death of RelA⁺/RelB⁻ CLL B-cells were higher than that of CLL B-cells from RelA⁺/RelB⁺ group when co-cultured with hBMSCs. RelA and RelB expression in CLL-B cells from the RelA⁺/RelB⁻ group was induced after co-cultured with hBMSCs for 48 h. RelB was reduced in the cytoplasm and increased in the nucleus in CLL-B cells from the RelA+/RelB+ group.

<b>CONCLUSIONb>The alternative NF-&kappa;B was indeed activated and presented heterogeneous in CLL B-cells from BM. Activation of RelB combined with RelA activity could provide the survival advantage to CLL B-cells from BM. Co-culture with hBMSCs could protect CLL-B cells through the induction of RelA and Rel B expressions.

Case-Control Studies ; Cell Nucleus ; metabolism ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; NF-kappa B p50 Subunit ; metabolism ; NF-kappa B p52 Subunit ; metabolism ; Transcription Factor RelA ; metabolism ; Transcription Factor RelB ; metabolism ; Tumor Cells, Cultured

<b>OBJECTIVEb>To investigate whether hepatitis B virus (HBV) can induce the expression of the host-encoded cytokine interleukin-32 (IL-32) and its effects on host signaling mechanisms related to HBV pathogenesis.

<b>METHODSb>A eukaryotic expression vector harboring an enhanced green fluorescent protein was constructed with HBV genomic sequences (pIRES2-HBV-EGFP) and transfected into HepG2 cells. In addition, the nuclear factor-kappa B (NF-kB) subunits, p50 and p65, were transfected respectively into HepG2 cells. In both cases, 48 hrs after transfection, IL-32 expression was determined at the mRNA and protein levels using real-time PCR and ELISA and western blot, respectively. The HepG2 cells transfected with pIRES2-HBV-EGFP were also treated with the NF-kB inhibitor SN50 at various concentrations, and the effects on IL-32 protein expression 48 hrs later were evaluated by western blot. Significance of between-group differences was assessed by the Student's t-test.

<b>RESULTSb>Transfection with pIRES2-HBV-EGFP led to significantly higher IL-23 expression than transfection with empty vector (mRNA: 2.8-fold higher and protein: 4.5-fold higher; both P less than 0.05). Transfection of p50 and p65 proteins led to significantly higher IL-32 expression (both P less than 0.05), and NF-kB activation was found to be required for HBV-induced IL-32 expression.

<b>CONCLUSIONb>IL-32 expression is induced by HBV in HepG2 cells. This host-encoded cytokine, and its downstream activation of NF-kB, may be involved in the pathogenesis of HBV, especially in the subsequent liver inflammation that accompanies HBV infection.

Genetic Vectors ; Hep G2 Cells ; metabolism ; Hepatitis B virus ; Host-Pathogen Interactions ; Humans ; Interleukins ; metabolism ; NF-kappa B p50 Subunit ; metabolism ; Transcription Factor RelA ; metabolism ; Transfection

Immuno-fluorescence technique can qualitatively determine certain nuclear translocation, of which NF-&kappa;B/ p65 implicates the activation of NF-&kappa;B signal pathways. Immuno-fluorescence analysis software with independent property rights is able to quantitatively analyze dynamic location of NF-&kappa;B/p65 by computing relative fluorescence units in nuclei and cytoplasm. We verified the quantitative analysis by Western Blot. When we applied the software to analysis of nuclear translocation in lipopolysaccharide (LPS) induced (0. 5 h, 1 h, 2 h, 4 h) primary human umbilical vein endothelial cells (HUVECs) , we found that nuclear translocation peak showed up at 2h as with calculated Western blot verification results, indicating that the inventive immuno-fluorescence analysis software can be applied to the quantitative analysis of immuno-fluorescence.
Active Transport, Cell Nucleus ; Cell Nucleus ; metabolism ; Cytoplasm ; metabolism ; Fluorescent Antibody Technique ; Human Umbilical Vein Endothelial Cells ; Humans ; NF-kappa B p50 Subunit ; metabolism ; Software

<b>OBJECTIVEb>To explore the correlation between MBL ExonI 54 and NF&kappa;B1-94ins/del ATTG polymorphism and fever during neutropenia in patients with acute leukaemia (AL) (except M3) after first chemotherapy in Chinese Han population.

<b>METHODSb>Blood samples obtained from 76 fever patients with AL during neutropenia episodes were detected to analyse single nucleotide polymorphism (SNP) in the MBL ExonI 54 and NF&kappa;B1-94ins/del ATTG gene, and analyse the correlation between above-mentioned 2 polymorphisms and fever during neutropenia of AL patients after chemotherapy.

<b>RESULTSb>In 76 patients, no correlation were found between MBL ExonI 54 and NF&kappa;B1-94ins/del ATTG polymorphism and fever during neutropenia in patients with acute leukaemia after chemotherapy (P > 0.05). No significant relation were found in sex, age, underlying disease, disease status or degrees of neutropenia in febrile neutropenia between MBL ExonI 54 and NF&kappa;B1-94ins/del ATTG polymorphism (P > 0.05). However, patients with MBL ExonI 54 mutation presented longer febrile duration with a median of 5 days compared to 3 days of patients with wildtype MBL ExonI 54 genotype (P < 0.05).

<b>CONCLUSIONSb>There is no clear correlation between MBL ExonI 54 and NF&kappa;B1-94ins/del ATTG polymorphism and fever during neutropenia in patients with acute leukaemia after chemotherapy. However, the patients with MBL ExonI 54 mutation have been observed to present a longer febrile duration.

Acute Disease ; Exons ; Fever ; Genotype ; Humans ; INDEL Mutation ; Leukemia ; drug therapy ; genetics ; Mannose-Binding Lectin ; genetics ; NF-kappa B p50 Subunit ; genetics ; Neutropenia ; Polymorphism, Single Nucleotide

<b>OBJECTIVEb>To explore the expression of high mobility group box protein 1 (HMGB1) and nuclear factor-kappa B (NF-&kappa;B) in patients with acute leukemia and its significance.

<b>METHODb>20 samples of bone marrow and peripheral blood from each acute leukemia groups (newly diagnozed, relapsed and complete remission groups) and 20 samples as control from patients with no-hematologic malignancies were collected. The expression level of HMGB1 in peripheral blood plasma was determined by ELISA; HMGB1 and NF-&kappa;B level in mononuclear cells were examined by RT-PCR. Western blot was used to determine HMGB1 and NF-&kappa;B protein levels. HMGB1 and NF-&kappa;B in bone marrow smears were determined by immnohistochemistry method (IHC).

<b>RESULTSb>The expression level of HMGB1 obviously increased in patients of newly diagnosed and relapsed groups, as compared with control group there was statistical significance (P < 0.05), but there was no obvious difference in expression level of HMGB1 between complete remission group and control group (P > 0.05). The expression level of HMGB1 and NF-kB in monnuclear cells of bone marrow in newly-diagnosed group and relapsed group was significantly higher than that in control group (P < 0.05), but the expression levels of HMGB1 and NF-kB in complete remisson group did not change (P > 0.05). The results of immnohistochemistry method indicated that the possitive expression of HMGB1 and NF-kB maily was found in bone marrow smears of newly diagnosed and relapsed groups.

<b>CONCLUSIONb>HMGB1 is overexpressed in acute leukemia, which may be involved in the occurrence and development of acute leukemia by activating the NF-&kappa;B signaling pathway, HMGB1 may be a important index for observing therapeutic effectiveness and predicting recurrence of acute leukemia.

Acute Disease ; Blotting, Western ; Bone Marrow ; Case-Control Studies ; HMGB1 Protein ; metabolism ; Humans ; Leukemia ; diagnosis ; metabolism ; NF-kappa B p50 Subunit ; metabolism ; Remission Induction ; Signal Transduction

In this study, immunohistochemistry and Western blot were used to determine whether the expression of NF-kappaB in the hippocampus of prenatally stressed offspring rats is gender-dependent. The results were as follows: In the female offspring rats, the expressions of p65 in the hippocampal dentate gyrus in mid-term stress (MS) and late-term stress (LS) groups were significantly less than that in the control group (P<0.01). There was a significant difference between MS and LS groups (P<0.01). The expressions of p50 in all regions of hippocampus in MS and LS groups were significantly more than that in the control group (P<0.01). A significant difference was also present between MS and LS groups (P<0.01). In the male offspring rats, the expressions of p65 in the hippocampal dentate gyrus in MS and LS groups were evidently more than that in the control group (P<0.01). There was a significant difference between MS and LS groups (P<0.01). The expressions of p50 in all regions of hippocampus in MS and LS groups were significantly less than that in the control group (P<0.05, P<0.01). There was also a significant difference in p65 expression between MS and LS groups (P<0.01). In addition, in the control group the expressions of p65 in the hippocampal dentate gyrus of female offspring rats were significantly more than that of male ones (P<0.01). However, in LS group the expressions of p65 in the hippocampal dentate gyrus of female offspring rats were significantly less than that of male ones (P<0.01). Moreover, there was no significant difference in p65 expression between female and male offspring rats in MS group. In the control group the gender difference in the expression of p50 was only observed in hippocampal CA1 (P<0.01). The expressions of p50 in all regions of hippocampus of female offspring rats were significantly more than that of male ones in LS group (P<0.01). There was no significant difference in p50 expression between female and male offspring rats in MS group. The results of Western blot were similar to those of immunohistochemical study. These results indicate that prenatal stress in different gestational periods significantly affects the expressions of p65 and p50 in hippocampus, and this effect is gender-dependent. This may be one of the mechanisms underlying the gender difference in the ability of learning and memory of the prenatally stressed offspring rats.
Animals ; Female ; Hippocampus ; metabolism ; Male ; NF-kappa B p50 Subunit ; metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Sex Factors ; Stress, Physiological ; Transcription Factor RelA ; metabolism