Transcriptional regulation of TNF/LT locus in immune cells

Shebzukhov, Yu. V.; Kuprash, Dmitry V.

doi:10.1134/s0026893311010110

Cited by 6 publications

(8 citation statements)

References 95 publications

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“…The TNF‐α gene promoter, third intron and enhancer located immediately after the gene contain multiple transcription‐factor‐binding sites. These binding sites regulate transcription through binding with members of transcription factor families as nuclear factor of activated T cells (NFAT), nuclear factor‐κB (NF‐κB), Ets, interferon‐regulating factor and CCAAT/enhancer‐binding protein α 26 . Co‐regulators are transcriptional regulators that, in contrast to transcription factors, lack DNA‐binding properties.…”

Section: Regulation Of the Production Processing And Signaling Of Tnmentioning

confidence: 99%

Regulation of TNF‐α with a focus on rheumatoid arthritis

et al. 2013

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Cytokines and chemokines represent two important groups of proteins that control the human immune system. Dysregulation of the network in which these immunomodulators function can result in uncontrolled inflammation, leading to various diseases including rheumatoid arthritis (RA), characterized by chronic inflammation and bone erosion. Potential triggers of RA include autoantibodies, cytokines and chemokines. The tight regulation of cytokine and chemokine production, and biological activity is important. Tumor necrosis factor-α (TNF-α) is abundantly present in RA patients' serum and the arthritic synovium. This review, therefore, discusses first the role and regulation of the major proinflammatory cytokine TNF-α, in particular the regulation of TNF-α production, post-translational processing and signaling of TNF-α and its receptors. Owing to the important role of TNF-α in RA, the TNF-α-producing cells and the dynamics of its expression, the direct and indirect action of this cytokine and possible biological therapy for RA are described.

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Section: Regulation Of the Production Processing And Signaling Of Tnmentioning

confidence: 99%

Regulation of TNF‐α with a focus on rheumatoid arthritis

et al. 2013

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“…Tumor necrosis factor (TNF) is a pleiotropic cytokine expressed by various types of lymphoid and myeloid cells, including T cells, B cells, NK cells, monocytes, macrophages, DCs, and mast cells (reviewed in [1,2]). TNF is involved in development, homeostasis, and activation of the immune system [3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…Numerous reports also supported the involvement of the NF-κB family members in transcriptional regulation of the TNF gene in macrophages, in spite of the lack of canonical high-affinity NF-κB binding sites within the proximal TNF promoter [32][33][34][35][36][37][38][39]. However, specific role of NF-κB family members in regulation of the TNF gene is still being debated ( [1,2] and Discussion section). In murine T cells, members of the NF-κB family were shown to bind to the distal part of the TNF promoter [40] and to the enhancer element immediately downstream of the TNF gene (3 -TNF enhancer) [24], but the functional significance of these interactions is not clear.…”

Section: Introductionmentioning

confidence: 99%

Dynamic changes in chromatin conformation at theTNFtranscription start site inThelper lymphocyte subsets

et al. 2013

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Tumor necrosis factor (TNF) is one of the key primary response genes in the immuneKeywords: Chromatin conformation r Th cells r T lymphocyte r TNF r Transcription start site Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionTumor necrosis factor (TNF) is a pleiotropic cytokine expressed by various types of lymphoid and myeloid cells, including T cells, B cells, NK cells, monocytes, macrophages, DCs, and mast cells (reviewed in [1,2]). TNF is involved in development, homeostasis, and activation of the immune system [3][4][5][6][7][8]. Physiological functions mediated by TNF depend on the cellular sources and the molecular form of this cytokine [9][10][11]. In particular, TNF produced by macrophages and T cells plays different roles in immune and inflammatory reactions [9,10]. TNF is the primary response gene in macrophages where it has a permissive chromatin conformation [12,13]. Even without stimulation, the proximal TNF Correspondence: Dr. Yury V. Shebzukhov e-mail: shebzukhov@drfz.de promoter and transcription start site (TSS) have an open chromatin configuration in primary monocytes and macrophages and in the majority of tested myelomonocytic cell lines [14][15][16][17][18][19][20][21][22]. Various T-cell subsets produce different amounts of TNF in correlation with their pathophysiological potential [23]. Earlier studies [24] as well as recent advances in high-throughput analysis of DNaseI chromatin accessibility indicate that the proximal part of the TNF promoter in T cells is open (Supporting Information Fig. 1); however, in contrast to macrophages, the TSS of TNF in T cells acquires open chromatin conformation only after activation or polarization under Th1 or Th17 (where Th is T helper) conditions. TNF gene expression in T cells is regulated by the NFAT and AP-1 families of transcription factors; in particular, activation of the proximal TNF promoter region involves functional interactions with the transcription factors NFATc2 and c-Jun [25][26][27][28][29][30][31]. Numerous reports also supported the involvement of the NF-κB family members in transcriptional regulation of the TNF gene inwww.eji-journal.eu 252Yury V. Shebzukhov et al. Eur. J. Immunol. 2014. 44: 251-264 macrophages, in spite of the lack of canonical high-affinity NF-κB binding sites within the proximal TNF promoter [32][33][34][35][36][37][38][39]. However, specific role of NF-κB family members in regulation of the TNF gene is still being debated ([1, 2] and Discussion section). In murine T cells, members of the NF-κB family were shown to bind to the distal part of the TNF promoter [40] and to the enhancer element immediately downstream of the TNF gene (3 -TNF enhancer) [24], but the functional significance of these interactions is not clear.Here, we demonstrate the difference in chromatin structure around TNF TSS between T cells and macrophages. We further show that active forms of c-Jun and NFATc2 transcription factors are involved in chromatin remodeling oc...

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“…A number of studies have implicated several transcription factors in TNF‐α gene regulation, such as NF‐κB and NFA, and others including interferon regulatory factor (IRF) families, Ets, C/EBPα [Falvo et al, 2010; Shebzukhov and Kuprash, 2011]. In macrophages, NF‐κB is undoubtedly considered the most important transcription factor, on the other hand, TNF‐α is described as one of the classical NF‐κB target pro‐inflammatory cytokine [Blackwell and Christman, 1997].…”

Section: Discussionmentioning

confidence: 99%

Kallikrein‐binding protein inhibits LPS‐induced TNF‐α by upregulating SOCS3 expression

Dai

Lü

Yang

et al. 2013

J of Cellular Biochemistry

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Kallikrein-binding protein (KBP) was previously identified as a serpin family member with specific inhibitory effect on tissue kallikrein and angiogenesis, while there is little knowledge about the effects on inflammation. The aim of this study is to investigate whether KBP can suppress LPS-induced inflammatory process. Our results showed that both recombinant KBP and KBP overexpression inhibited LPS-stimulated TNF-α transcription and translation in macrophage cell line RAW264.7 and primary macrophages. Furthermore, KBP treatment protected mice from endotoxin shock and repressed serum TNF-α production, increasing survival rate of mice from 10% to 50% when compared to LPS alone. Moreover, qPCR and Western blot analysis demonstrated that both suppressor of cytokine signaling 3 (SOCS3) transcription and translation were induced by KBP treatment in the present of LPS. RNA interference assay and luciferase assay showed that SOCS3 was responsible for the down-regulation of TNF-α by KBP, rather than NF-κB subunit p65 and β-catenin. Therefore, we demonstrated that KBP suppressed LPS-induced TNF-α production via upregulating SOCS3 expression. These results present the protective effects of KBP on LPS-induced inflammation and provide novel information for the anti-inflammation mechanism.

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Transcriptional regulation of TNF/LT locus in immune cells

Cited by 6 publications

References 95 publications

Regulation of TNF‐α with a focus on rheumatoid arthritis

Regulation of TNF‐α with a focus on rheumatoid arthritis

Dynamic changes in chromatin conformation at theTNFtranscription start site inThelper lymphocyte subsets

Kallikrein‐binding protein inhibits LPS‐induced TNF‐α by upregulating SOCS3 expression

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