Induction of Interleukin-8 Synthesis Integrates Effects on Transcription and mRNA Degradation from at Least Three Different Cytokine- or Stress-Activated Signal Transduction Pathways

Holtmann, Helmut; Winzen, Reinhard; Holland, Pamela M.; Eickemeier, Solveig; Hoffmann, É; Wallach, David; Malinin, Nikolay L.; Cooper, Jonathan A.; Resch, Klaus; Kracht, Michael

doi:10.1128/mcb.19.10.6742

Cited by 279 publications

(285 citation statements)

References 66 publications

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“…[24][25][26] In the studies shown in Table 1, we examined the effect of the ERK, JNK II, p38 MAPK and NF-kB alone or in combination with each of the other inhibitors. The NF-kB inhibitor alone markedly inhibited both MCP-1 and PGE 2 formation; In the presence of the ERK inhibitor plus either the JNK or the p38 MAPK inhibitor, a reproducible inhibition of MCP-1 formation and almost total inhibition of PGE 2 formation was seen in visceral explants.…”

Section: Methodsmentioning

confidence: 99%

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Fain

Madan

2005

Int J Obes

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BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte recruitment during inflammation whose plasma level is elevated in obesity. OBJECTIVE: The present studies were designed to examine the release of MCP-1 in primary culture by explants of visceral adipose tissue from morbidly obese women. RESULTS: Most of the MCP-1 released by adipose tissue explants was derived from the nonfat cells in adipose tissue. The release of MCP-1 by adipose tissue explants was upregulated almost five-fold between 3 and 48 h of incubation. Approximately half of this upregulation was due to the release of endogenous tumor necrosis factor a (TNFa) and IL-1b based on the ability of a combination of a soluble TNFa receptor (etanercept) and a blocking antibody against IL-1b to reduce MCP-1 release. The release of MCP-1 over 48 h was unaffected by insulin or dexamethasone but significantly reduced by the combination of both agents. MCP-1 release was reduced by 60% in the presence of an inhibitor of the nuclear factor kB (NF-kB) pathway. There were no significant effects of inhibitors of p44/42 mitogen-activated protein kinase (ERK), Jun N-terminal kinase (JNK) and p38 mitogenactivated protein kinase (p38 MAPK) pathways on MCP-1 release. However, inhibition of MCP-1 release in the presence of inhibitors of both the p38 MAPK and NF-kB pathways was greater than that seen with only the NF-kB inhibitor. DISCUSSION: The present data shows that MCP-1 formation is upregulated over a 48-h incubation of primary explants of visceral adipose tissue. Half of this upregulation is dependent upon endogenous TNFa and Il-1b and involves the p38 MAPK and NF-kB pathways.

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Section: Methodsmentioning

confidence: 99%

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Fain

Madan

2005

Int J Obes

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“…In contrast, our study clearly demonstrated that even though AP-1 activation was suppressed by EMSA following expression of the DN c-Jun, no suppression of IL-6 or IL-8 secretion was observed. Activation of the mitogen-activated protein (MAP) kinase pathway has been shown to contribute to both IL-6 and IL-8 expression (44,51,52). Inhibition of the p38 MAP kinase pathway in RA FLS, or the extracellular signal-related kinase-1/2 pathway in monocytes, suppressed IL-6 secretion without affecting NF-B activation (44,51).…”

Section: Discussionmentioning

confidence: 99%

Regulation of IL-6 and IL-8 Expression in Rheumatoid Arthritis Synovial Fibroblasts: the Dominant Role for NF-κB But Not C/EBPβ or c-Jun

Georganas

Liu

Perlman

et al. 2000

The Journal of Immunology

202

134

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Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) produce IL-6 and IL-8, which contribute to inflammation and joint damage. The promoters of both cytokines possess binding sites for NF-κB, C/EBPβ, and c-Jun, but the contribution of each to the regulation of IL-6 and IL-8 in RA FLS is unknown. We employed adenoviral-mediated gene delivery of a nondegradable IκBα, or dominant-negative versions of C/EBPβ or c-Jun, to determine the contribution of each transcription factor to IL-6 and IL-8 expression. Inhibition of NF-κB activation significantly reduced the spontaneous and IL-1β-induced secretion of IL-6 and IL-8 by RA FLS and the IL-1β-induced production of IL-6 and IL-8 by human dermal fibroblasts. Inhibition of C/EBPβ modestly reduced constitutive and IL-1β-induced IL-6 by RA FLS, but not by human dermal fibroblasts, and had no effect on IL-8. Inhibition of c-Jun/AP-1 had no effect on the production of either IL-6 or IL-8. Employing gel shift assays, NF-κB, C/EBPβ, and c-Jun were constitutively activated in RA FLS, but only NF-κB and c-Jun activity increased after IL-1β. The reduction of cytokines by IκBα was mediated through inhibition of NF-κB activation, which resulted in decreased IL-6 and IL-8 mRNA. NF-κB was essential for IL-6 expression, because fibroblasts in which both NF-κB p50/p65 genes were deleted failed to express IL-6 in response to IL-1. These findings document the importance of NF-κB for the regulation of the constitutive and IL-1β-stimulated expression of IL-6 and IL-8 by RA FLS and support the role of inhibition of NF-κB as a therapeutic goal in RA.

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“…It has been reported that the ERK pathway may activate IL-8 transcription in an NF-kB-independent fashion (Holtmann et al, 1999). We used PD98059, a specific inhibitor of the ERK pathway, to test its involvement in K13-induced IL-8 promoter activation.…”

Section: K13 Induces Il-8 Via Nf-jb Pathway Q Sun Et Almentioning

confidence: 99%

Induction of IL-8 expression by human herpesvirus 8 encoded vFLIP K13 via NF-κB activation

Sun

Matta

et al. 2006

Oncogene

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Induction of Interleukin-8 Synthesis Integrates Effects on Transcription and mRNA Degradation from at Least Three Different Cytokine- or Stress-Activated Signal Transduction Pathways

Cited by 279 publications

References 66 publications

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Regulation of IL-6 and IL-8 Expression in Rheumatoid Arthritis Synovial Fibroblasts: the Dominant Role for NF-κB But Not C/EBPβ or c-Jun

Induction of IL-8 expression by human herpesvirus 8 encoded vFLIP K13 via NF-κB activation

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