Transcriptional regulation of cytokine expression by diethyldithiocarbamate in human HL-60 promyelocytic leukemia cells

Schmalbach, Therese K.; Datta, Rakesh; Küfe, Donald; Sherman, Matthew L.

doi:10.1016/0006-2952(92)90021-a

Cited by 7 publications

(4 citation statements)

References 31 publications

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“…The same pattern of differential staining for the N-and C-terminal IL-1␣ segments was also seen in phorbol ester-stimulated human promyelocytic HL-60 leukemia cells (Fig. 3), indicating that selective targeting of the N-terminal IL-1␣ propiece also occurs in a nontransfected cell type capable of endogenous IL-1␣ synthesis and processing (26). A similar pattern of differential staining was also detected with phorbol ester-stimulated human promonocytic U937 cells (data not shown).…”

Section: Resultsmentioning

confidence: 67%

The N-terminal propiece of interleukin 1α is a transforming nuclear oncoprotein

Stevenson

Turck

Locksley

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

106

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Section: Resultsmentioning

confidence: 67%

The N-terminal propiece of interleukin 1α is a transforming nuclear oncoprotein

Stevenson

Turck

Locksley

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

106

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“…By contrast, PDTC completely inhibits human fibroblast ICAM-1 expression under similar conditions (40). Contrasting effects have also been reported in human monocytes and promyelocytic cells when antioxidant modulation of the TNF-␣ gene has been studied (39,42). Moreover, species specificity may account for some of the contrasting observations, since PDTC potentiates LPSinduced TNF-␣ gene expression in murine macrophages (43), yet attenuates it in human monocytes (39).…”

Section: Discussionmentioning

confidence: 85%

Pyrrolidine Dithiocarbamate Attenuates Endotoxin-induced Acute Lung Injury

Nathens

Bitar

Davreux

et al. 1997

Am J Respir Cell Mol Biol

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Lung injury in the acute respiratory distress syndrome (ARDS) is in part due to polymorphonuclear leukocyte (PMN)-mediated oxidative tissue damage. By means of nuclear factor-kappaB (NF-kappaB) activation, oxidants may also induce several genes implicated in the inflammatory response. The dithiocarbamates are antioxidants with potent inhibitory effects on NF-kappaB. We postulated that the pyrrolidine derivative pyrrolidine dithiocarbamate (PDTC) would attenuate lung injury following intratracheal challenge with endotoxin (lipopolysaccharide; LPS) through its effect as an antioxidant and inhibitor of gene activation. Rats were given PDTC (1 mmole/kg) by intraperitoneal injection, followed by intratracheal administration of LPS. The transpulmonary flux of [125I] albumin (permeability index; PI) was used as a measure of lung injury. Northern blot analysis of total lung RNA was performed to assess induction of tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) messenger RNA (mRNA) as markers of NF-kappaB activation. The effect of in vivo treatment with PDTC on LPS-induced NF-kappaB DNA binding activity in macrophage nuclear extracts was evaluated with the electrophoretic mobility shift assay (EMSA). PDTC administration attenuated LPS-induced increases in lung permeability (PI = 0.16 +/- 0.02 for LPS versus 0.06 +/- 0.01 for LPS + PDTC; P < 0.05). TNF-alpha levels and PMN counts in bronchoalveolar lavage fluid (BALF) were unaffected, as were whole-lung TNF-alpha and ICAM-1 mRNA expression. PDTC had no effect on NF-kappaB activation as evaluated with EMSA. PDTC reduced lung lipid peroxidation as assessed by levels of malondialdehyde, without reducing neutrophil oxidant production. We conclude that PDTC attenuates LPS-induced acute lung injury. This effect occurs independently of any effect on NF-kappaB. PDTC reduces oxidant-mediated cellular injury, as demonstrated by a reduction in the accumulation of malondialdehyde. Administration of PDTC may represent a novel approach to limiting neutrophil-mediated oxidant injury.

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“…EMSAs and CAT assays supported an involvement of AP-1 in the antioxidant response by the human NQOI ARE (Li and Jaiswal, 1992a,b). Schmalbach et al (1992) have observed that IL-1 and TNF genes are induced 3 h after incubation with the diethyl derivative of dithiocarbamate. A point mutation analysis suggested an ARE consensus motif in AA AAA4 Fig.…”

Section: *mentioning

confidence: 99%

“…It will be interesting to find out whether PDTC and thioredoxin can also induce NQO, and GST Ya expression and, on the other hand, whether BHA and j-naphthoflavone induce a classical TRE-controlled CAT reporter gene. Schmalbach et al (1992) have observed that IL-1 and TNF genes are induced 3 h after incubation with the diethyl derivative of dithiocarbamate. It is possible that the AP-1 sites in the 5 '-flanking regions of these genes were involved in this antioxidant response.…”

Section: Transient Expression Of Human Thioredoxin Activates Ap-1 Butmentioning

confidence: 99%

H2O2 and antioxidants have opposite effects on activation of NF-kappa B and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor.

Meyer¹,

Schreck²,

Baeuerle³

1993

The EMBO Journal

1,258

659

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We show that AP‐1 is an antioxidant‐responsive transcription factor. DNA binding and transactivation by AP‐1 were induced in HeLa cells upon treatment with the antioxidants pyrrolidine dithiocarbamate (PDTC) and N‐acetyl‐L‐cysteine (NAC), and upon transient expression of the antioxidative enzyme thioredoxin. While PDTC and NAC enhanced DNA binding and transactivation of AP‐1 in response to phorbol ester, the oxidant H2O2 suppressed phorbol ester activation of the factor. H2O2 on its own was only a weak inducer of AP‐1. Activation of AP‐1 by PDTC was dependent on protein synthesis and involved transcriptional induction of c‐jun and c‐fos genes. Transcriptional activation of c‐fos by PDTC was conferred by the serum response element, suggesting that serum response factor and associated proteins function as primary antioxidant‐responsive transcription factors. In the same cell line, the oxidative stress‐responsive transcription factor NF‐kappa B behaved in a manner strikingly opposite to AP‐1. DNA binding and transactivation by NF‐kappa B were strongly activated by H2O2, while the antioxidants alone were ineffective. H2O2 potentiated the activation of NF‐kappa B by phorbol ester, while PDTC and NAC suppressed PMA activation of the factor. PDTC did not influence protein kinase C (PKC) activity and PKC activation by PMA, indicating that the antioxidant acted downstream of and independently from PKC.

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Transcriptional regulation of cytokine expression by diethyldithiocarbamate in human HL-60 promyelocytic leukemia cells

Cited by 7 publications

References 31 publications

The N-terminal propiece of interleukin 1α is a transforming nuclear oncoprotein

The N-terminal propiece of interleukin 1α is a transforming nuclear oncoprotein

Pyrrolidine Dithiocarbamate Attenuates Endotoxin-induced Acute Lung Injury

H2O2 and antioxidants have opposite effects on activation of NF-kappa B and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor.

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