TNF-ALPHA-STIMULATED REGULATION OF NF-κB-DEPENDENT GENE TRANSCRIPTION IS MEDIATED BY P38 AND ERK MAP KINASES IN ISOLATED ACINAR CELLS

Abstract In highly purified human polymorphonuclear leukocyte (PMN) preparations containing less than 0.1% contaminating monocytes, significant amounts of interleukin-8 (IL-8) and small amounts of IL-1 alpha, IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha) were produced by lipopolysaccharide (LPS) stimulation. Contrary to published reports, IL- 6 production could not be detected. IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-8, and TNF-alpha in LPS-stimulated PMNs, as it did in human blood mononuclear cell (MNC) preparations enriched in monocytes. Subsequent investigation of cytokine synthesis inhibitory effect of IL-10 on PMNs was focused on IL-8. IL-10 inhibited IL-8 synthesis in a dose-dependent manner and, in this regard, it was more potent than IL-4 and transforming growth factor-beta 1 (TGF-B1). In both MNCs and PMNs, degradation of LPS-induced IL-8 mRNA was enhanced by IL-10. Furthermore, as determined by nuclear run-on assays, IL-10 inhibited LPS-induced transcription of IL-8 gene in MNCs. However, in PMNs, run-on assays could not reliably detect IL-8 gene transcription. These results provide the first evidence that the human peripheral neutrophil is a target for inhibition of cytokine synthesis by IL-10, and that IL-10 acts by affecting both gene transcription and mRNA stability.

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Transforming growth factor β activates mitogen-activated (MAP) kinases in pancreatic acinar cells

Gastroenterology ◽

10.1016/s0016-5085(98)82025-8 ◽

1998 ◽

Vol 114 ◽

pp. A500

Author(s):

Diane Simeone ◽

Claus Schaefer ◽

Barbara Nicke ◽

Trinh Pham ◽

Craig Logsdon

Keyword(s):

Growth Factor ◽

Map Kinases ◽

Transforming Growth Factor ◽

Acinar Cells ◽

Transforming Growth Factor Β ◽

Pancreatic Acinar Cells

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Interleukin-10 inhibits interleukin-8 production in human neutrophils

Blood ◽

10.1182/blood.v83.9.2678.bloodjournal8392678 ◽

1994 ◽

Vol 83 (9) ◽

pp. 2678-2683 ◽

Cited By ~ 5

Author(s):

P Wang ◽

P Wu ◽

JC Anthes ◽

MI Siegel ◽

RW Egan ◽

...

Keyword(s):

Gene Transcription ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Interleukin 10 ◽

Interleukin 8 ◽

Tnf Alpha ◽

Human Neutrophils ◽

Dependent Manner ◽

Necrosis Factor Alpha ◽

Cytokine Synthesis

In highly purified human polymorphonuclear leukocyte (PMN) preparations containing less than 0.1% contaminating monocytes, significant amounts of interleukin-8 (IL-8) and small amounts of IL-1 alpha, IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha) were produced by lipopolysaccharide (LPS) stimulation. Contrary to published reports, IL- 6 production could not be detected. IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-8, and TNF-alpha in LPS-stimulated PMNs, as it did in human blood mononuclear cell (MNC) preparations enriched in monocytes. Subsequent investigation of cytokine synthesis inhibitory effect of IL-10 on PMNs was focused on IL-8. IL-10 inhibited IL-8 synthesis in a dose-dependent manner and, in this regard, it was more potent than IL-4 and transforming growth factor-beta 1 (TGF-B1). In both MNCs and PMNs, degradation of LPS-induced IL-8 mRNA was enhanced by IL-10. Furthermore, as determined by nuclear run-on assays, IL-10 inhibited LPS-induced transcription of IL-8 gene in MNCs. However, in PMNs, run-on assays could not reliably detect IL-8 gene transcription. These results provide the first evidence that the human peripheral neutrophil is a target for inhibition of cytokine synthesis by IL-10, and that IL-10 acts by affecting both gene transcription and mRNA stability.

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DNA Damage Induces Dynamic Associations of BRD4/P-TEFb With Chromatin and Modulates Gene Transcription in a BRD4-Dependent and -Independent Manner

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2020.618088 ◽

2020 ◽

Vol 7 ◽

Author(s):

Yawei Song ◽

Gongcheng Hu ◽

Jinping Jia ◽

Mingze Yao ◽

Xiaoshan Wang ◽

...

Keyword(s):

Rna Polymerase Ii ◽

Gene Transcription ◽

Map Kinases ◽

Transcriptional Elongation ◽

Dependent Manner ◽

Rna Seq ◽

Mitotic Chromosomes ◽

Uv Treatment ◽

Independent Manner ◽

Uv Stress

The bromodomain-containing protein BRD4 has been thought to transmit epigenetic information across cell divisions by binding to both mitotic chromosomes and interphase chromatin. UV-released BRD4 mediates the recruitment of active P-TEFb to the promoter, which enhances transcriptional elongation. However, the dynamic associations between BRD4 and P-TEFb and BRD4-mediated gene regulation after UV stress are largely unknown. In this study, we found that BRD4 dissociates from chromatin within 30 min after UV treatment and thereafter recruits chromatin. However, P-TEFb binds tightly to chromatin right after UV treatment, suggesting that no interactions occur between BRD4 and P-TEFb within 30 min after UV stress. BRD4 knockdown changes the distribution of P-TEFb among nuclear soluble and chromatin and downregulates the elongation activity of RNA polymerase II. Inhibition of JNK kinase but not other MAP kinases impedes the interactions between BRD4 and P-TEFb. RNA-seq and ChIP assays indicate that BRD4 both positively and negatively regulates gene transcription in cells treated with UV stress. These results reveal previously unrecognized dynamics of BRD4 and P-TEFb after UV stress and regulation of gene transcription by BRD4 acting as either activator or repressor in a context-dependent manner.

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EGF receptor mRNA and protein in rat lacrimal acinar cells: evidence of its EGF-dependent phosphotyrosilation

AJP Cell Physiology ◽

10.1152/ajpcell.1996.270.4.c1164 ◽

1996 ◽

Vol 270 (4) ◽

pp. C1164-C1174 ◽

Cited By ~ 12

Author(s):

H. Marechal ◽

H. Jammes ◽

B. Rossignol ◽

P. Mauduit

Keyword(s):

Membrane Proteins ◽

Gene Transcription ◽

Acinar Cell ◽

Lacrimal Gland ◽

Blot Analysis ◽

Egf Receptor ◽

Receptor Gene ◽

Acinar Cells ◽

Polymerase Chain Reaction Analysis ◽

Lacrimal Acinar Cells

This study was designed to demonstrate the presence of the epidermal growth factor (EGF) receptor in the rat exorbital lacrimal gland. EGF receptor gene transcription was demonstrated 1) by reverse transcription-polymerase chain reaction analysis of lacrimal gland and acinar cells from RNA with a set of specific primers deduced from the rat EGF receptor sequence and 2) by Northern blot analysis of rat lacrimal gland mRNA. Lacrimal acinar cell preparations contain a low but detectable amount of specific 125I-EGF binding sites and efficiently internalize the ligand on binding at 37 degrees C. A sheep polyclonal antibody, directed against the human EGF receptor, detects a protein of 170 kDa by Western blot analysis of membrane proteins of the whole gland. This protein can be immunoprecipitated by the same antibody from whole gland membrane proteins as well as from solubilized acinar cells. Incubations of acinar cells in the presence of EGF results in an increased content of tyrosine-phosphorylated residues in immunoprecipitated 170-kDa protein. Taken together, these results demonstrate for the first time both EGF receptor gene transcription and protein expression in a lacrimal tissue, i.e., the rat exorbital lacrimal gland. These results also suggest a specific cellular location of the EGF receptor in a cell population contained in acinar cell preparations.

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Differential regulation of human B-lymphocyte tumor necrosis factor- alpha (TNF-alpha) and lymphotoxin (TNF-beta) production by protein phosphatase 1 and 2A inhibitor

Blood ◽

10.1182/blood.v82.9.2806.bloodjournal8292806 ◽

1993 ◽

Vol 82 (9) ◽

pp. 2806-2812

Author(s):

HZ Xia ◽

CC Kannapell ◽

SM Fu ◽

SS Sung

Keyword(s):

Tumor Necrosis Factor ◽

Gene Transcription ◽

Okadaic Acid ◽

Tumor Necrosis ◽

B Lymphocyte ◽

Cytokine Production ◽

Tnf Alpha ◽

Mrna Accumulation ◽

Necrosis Factor Alpha ◽

Necrosis Factor

Tumor necrosis factor (TNF) and lymphotoxin (LT; TNF-beta) are major cytokines produced by B lymphocytes. Stimulation by okadaic acid, a phosphatase 1 and 2A inhibitor, markedly increased TNF mRNA accumulation and cytokine production. On the other hand, the accumulation of LT mRNA was not affected by okadaic acid despite structural and functional similarities between TNF and LT. The increase in TNF mRNA accumulation was due to the stimulation of gene transcription and a marked stabilization of this mRNA. The binding activities of the transcription factors AP-1 and AP-2 and NF kappa B, which regulates TNF gene transcription, were also stimulated by okadaic acid. In addition, okadaic acid was shown to increase TNF production at the protein level. These results show the importance of protein phosphatases in the regulation of cytokine production in B cells, and further identifies differences in the regulation of TNF-alpha and LT production.

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Activity-dependent calcium signaling and ERK-MAP kinases in neurons: A link to structural plasticity of the nucleus and gene transcription regulation

Cell Calcium ◽

10.1016/j.ceca.2010.11.009 ◽

2011 ◽

Vol 49 (5) ◽

pp. 296-305 ◽

Cited By ~ 80

Author(s):

J. Simon Wiegert ◽

Hilmar Bading

Keyword(s):

Calcium Signaling ◽

Transcription Regulation ◽

Gene Transcription ◽

Map Kinases ◽

Structural Plasticity ◽

Gene Transcription Regulation ◽

Activity Dependent

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Differential regulation of human B-lymphocyte tumor necrosis factor- alpha (TNF-alpha) and lymphotoxin (TNF-beta) production by protein phosphatase 1 and 2A inhibitor

Blood ◽

10.1182/blood.v82.9.2806.2806 ◽

1993 ◽

Vol 82 (9) ◽

pp. 2806-2812 ◽

Cited By ~ 6

Author(s):

HZ Xia ◽

CC Kannapell ◽

SM Fu ◽

SS Sung

Keyword(s):

Tumor Necrosis Factor ◽

Gene Transcription ◽

Okadaic Acid ◽

Tumor Necrosis ◽

B Lymphocyte ◽

Cytokine Production ◽

Tnf Alpha ◽

Mrna Accumulation ◽

Necrosis Factor Alpha ◽

Necrosis Factor

Abstract Tumor necrosis factor (TNF) and lymphotoxin (LT; TNF-beta) are major cytokines produced by B lymphocytes. Stimulation by okadaic acid, a phosphatase 1 and 2A inhibitor, markedly increased TNF mRNA accumulation and cytokine production. On the other hand, the accumulation of LT mRNA was not affected by okadaic acid despite structural and functional similarities between TNF and LT. The increase in TNF mRNA accumulation was due to the stimulation of gene transcription and a marked stabilization of this mRNA. The binding activities of the transcription factors AP-1 and AP-2 and NF kappa B, which regulates TNF gene transcription, were also stimulated by okadaic acid. In addition, okadaic acid was shown to increase TNF production at the protein level. These results show the importance of protein phosphatases in the regulation of cytokine production in B cells, and further identifies differences in the regulation of TNF-alpha and LT production.

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