Transcription of promoter from the human APRIL gene regulated by Sp1 and NF-kB

Xu, Jianming; Wf, Ding; Kk, Shao; Xd, Wang; Gh, Wang; Hq, Li; Hm, Wang

doi:10.4149/neo_2012_044

Cited by 11 publications

(7 citation statements)

References 24 publications

(26 reference statements)

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“…It has been reported that NF-κB serves as a transcriptional factor for April gene expression, 24 and EGFR signaling mediates NF-κB activation. 25–27 We examined whether p40 activated NF-κB and whether EGFR-dependent APRIL expression by p40 was through activating NF-κB.…”

Section: Resultsmentioning

confidence: 99%

An LGG-derived protein promotes IgA production through upregulation of APRIL expression in intestinal epithelial cells

et al. 2017

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p40, a Lactobacillus rhamnosus GG (LGG)-derived protein, transactivates epidermal growth factor receptor (EGFR) in intestinal epithelial cells, leading to amelioration of intestinal injury and inflammation. To elucidate mechanisms by which p40 regulates mucosal immunity to prevent inflammation, this study aimed to determine the effects and mechanisms of p40 on regulation of a proliferation-inducing ligand (APRIL) expression in intestinal epithelial cells for promoting IgA production. p40 up-regulated April gene expression and protein production in mouse small intestine epithelial (MSIE) cells, which were inhibited by blocking EGFR expression and kinase activity. Enteroids from Egfrfl/fl , but not Egfrfl/fl-Vil-Cre mice with EGFR specifically deleted in intestinal epithelial cells, exhibited increased April gene expression by p40 treatment. p40-conditioned media from MSIE cells increased B cell class switching to IgA+ cells and IgA production, which was suppressed by APRIL receptor neutralizing antibodies. Treatment of B cells with p40 did not show any effects on IgA production. p40 treatment increased April gene expression and protein production in small intestinal epithelial cells, fecal IgA levels, IgA+B220+, IgA+CD19+, and IgA+ plasma cells in lamina propria of Egfrfl/fl, but not Egfrfl/fl-Vil-Cre mice. Thus, p40 up-regulates EGFR-dependent APRIL production in intestinal epithelial cells, which may contribute to promoting IgA production.

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Section: Resultsmentioning

confidence: 99%

An LGG-derived protein promotes IgA production through upregulation of APRIL expression in intestinal epithelial cells

et al. 2017

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“…injection of adult mice (62). NF-κB is important for promoting transcription of Tnfsrf13 (the gene that encodes APRIL) (63) and Tnfsrf13b (the gene that encodes BAFF) in macrophages (64). It is therefore possible that enhanced NF-κB translocation induced by LT-K63 directly affects the production of APRIL and BAFF that contribute to enhanced activation of B cells (Figures 3, 5) and their prolonged survival (Figure 8).…”

Section: Discussionmentioning

confidence: 99%

LT-K63 Enhances B Cell Activation and Survival Factors in Neonatal Mice That Translates Into Long-Lived Humoral Immunity

et al. 2020

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Adjuvants enhance magnitude and duration of immune responses induced by vaccines. In this study we assessed in neonatal mice if and how the adjuvant LT-K63 given with a pneumococcal conjugate vaccine, Pnc1-TT, could affect the expression of tumor necrosis factor receptor (TNF-R) superfamily members, known to be involved in the initiation and maintenance of antibody responses; B cell activating factor receptor (BAFF-R) and B cell maturation antigen (BCMA) and their ligands, BAFF, and a proliferation inducing ligand (APRIL). Initially we assessed the maturation status of different B cell populations and their expression of BAFF-R and BCMA. Neonatal mice had dramatically fewer B cells than adult mice and the composition of different subsets within the B cell pool differed greatly. Proportionally newly formed B cells were most abundant, but they had diminished BAFF-R expression which could explain low proportions of marginal zone and follicular B cells observed. Limited BCMA expression was also detected in neonatal pre-plasmablasts/plasmablasts. LT-K63 enhanced vaccine-induced BAFF-R expression in splenic marginal zone, follicular and newly formed B cells, leading to increased plasmablast/plasma cells, and their enhanced expression of BCMA in spleen and bone marrow. Additionally, the induction of BAFF and APRIL expression occurred early in neonatal mice immunized with Pnc1-TT either with or without LT-K63. However, BAFF + and APRIL + cells in spleens were maintained at a higher level in mice that received the adjuvant. Furthermore, the early increase of APRIL + cells in bone marrow was more profound in mice immunized with vaccine and adjuvant. Finally, we assessed, for the first time in neonatal mice, accessory cells of the plasma cell niche in bone marrow and their secretion of APRIL. We found that LT-K63 enhanced the frequency and APRIL expression of eosinophils, macrophages, and megakaryocytes, which likely contributed to plasma cell survival, even though APRIL + cells showed a fast decline. All this was associated with enhanced, sustained Aradottir Pind et al. LT-K63 and B-cell Survival Mechanisms vaccine-specific antibody-secreting cells in bone marrow and persisting vaccine-specific serum antibodies. Our study sheds light on the mechanisms behind the adjuvanticity of LT-K63 and identifies molecular pathways that should be triggered by vaccine adjuvants to induce sustained humoral immunity in early life.

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“…Phorbol 12‐myristate 13 acetate (PMA) induced an increase in the transcriptional activity of SP1 through the deacetylation of SP1, and also provoked the ectodomain shedding of HB‐EGF; it also increased the expression of HB‐EGF . Additionally, NF‐ κ B induced the expression of HB‐EGF, and the NF‐ κ B and SP1 binding sequence was shown to be the same GC‐rich element in colon cancer cells . This evidence suggests that SP1 augments the expression of HB‐EGF through the deacetylation of SP1 or via an interaction with NF‐ κ B.…”

Section: Discussionmentioning

confidence: 99%

Contribution of transcription factor, SP1, to the promotion of HB‐EGF expression in defense mechanism against the treatment of irinotecan in ovarian clear cell carcinoma

et al. 2014

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Ovarian clear cell carcinoma (OCCC) is a worst histological subtype than other ovarian malignant tumor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. The aims of this study were to validate the efficacy of HB-EGF–targeted therapy for OCCC and to identify the transcription factor that contributed to the induction of HB-EGF by SN38 treatment in OCCC cells. HB-EGF was highly expressed in OCCC cells, and an increase of HB-EGF was induced by SN38 which had only antitumor effect among conventional anticancer agents on OCCC. A specific inhibitor of HB-EGF, a cross-reacting material 197 (CRM197), led to a synergistic increase in the number of apoptotic OCCC cells with the treatment of SN38. The luciferase assay with 5′-deletion promoter constructs identified a GC-rich element between −125 and −178 (the distal transcription start site was denoted +1) as a cis-regulatory region, and the treatment of SN38 induced luciferase activity in this region. An in silico and chromatin immunoprecipitation analysis estimated that SP1 bound to the cis-regulatory region of HB-EGF in OCCC cells. Real-time PCR and cell viability assays showed that the transfection of a small interfering RNA targeting SP1 suppressed the expression of HB-EGF induced by SN38, resulting in the enhanced sensitivity of SN38. Taken together, these results indicate that induction of HB-EGF expression contributed to defense mechanism against treatment of SN38 through the transcriptional activity of SP1 in OCCC cells.

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Transcription of promoter from the human APRIL gene regulated by Sp1 and NF-kB

Cited by 11 publications

References 24 publications

An LGG-derived protein promotes IgA production through upregulation of APRIL expression in intestinal epithelial cells

An LGG-derived protein promotes IgA production through upregulation of APRIL expression in intestinal epithelial cells

LT-K63 Enhances B Cell Activation and Survival Factors in Neonatal Mice That Translates Into Long-Lived Humoral Immunity

Contribution of transcription factor, SP1, to the promotion of HB‐EGF expression in defense mechanism against the treatment of irinotecan in ovarian clear cell carcinoma

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