Induction of a 26-kDa-protein mRNA in human cells treated with an interleukin-1-related, leukocyte-derived factor

Wit, L. De; Poupart, P.; Opdenakker, Ghislain; Damme, Jo Van; Billiau, Alfons

doi:10.1111/j.1432-1033.1985.tb09191.x

Cited by 163 publications

(59 citation statements)

References 24 publications

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“…Recently, it has been demonstrated that fibroblasts can produce cytokines when stimulated with immunomodulators such as lipopolysaccharide or phorbol myristate acetate [33] or with cytokines themselves [34]. Therefore, it cannot be excluded that the effects observed in our experiments could be partly due to cytokines secreted by the fibroblasts as a result of TNF stimulation.…”

Section: Sds-page Analysis Of Radiolabelled Collagens and Fibronectincontrasting

confidence: 39%

Tumor necrosis factor inhibits collagen and fibronectin synthesis in human dermal fibroblasts

et al. 1988

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Tumor necrosis factor (TNF) caused inhibition of collagen production by confluent cultures of human dermal fibroblasts in a dose-dependent manner. Concomitant increase of prostaglandin E2 release was observed as a result of TNF-induced cell activation.However, a blockade of the cyclooxygenase pathway of arachidonate metabolism by indomethacin did not abrogate the inhibitory effect of TNF on collagen synthesis, suggesting that this effect could be independent of prostaglandin metabolism.Gel electrophoresis of the newly synthesized macromolecules from the culture media showed that both type I and type III collagens as well as fibronectin were affected by the inhibition.Electrophoresis of cell layerassociated proteins demonstrated that the reduction in amounts of collagen and fibronectin in the medium did not result from an intracellular accumulation of these macromolecules. Production of procollagens was reduced in parallel to that of collagens, suggesting that the effect of TNF is exerted before the processing steps of procollagens.These results clearly show that TNF could play a role in modulation of matrix deposition by fibroblasts during inflammatory processes.Tumor necrosis factor; Collagen; Fibronectin; Prostaglandin E,; (Dermal fibroblast)

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Section: Sds-page Analysis Of Radiolabelled Collagens and Fibronectincontrasting

confidence: 39%

Tumor necrosis factor inhibits collagen and fibronectin synthesis in human dermal fibroblasts

et al. 1988

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“…IL-6 is induced in various cell types by a plethora of activators. Among the strongest and first identified are the proinflammatory cytokines tumor necrosis factor (TNF) (21) and IL-1 (22). Expression of IL-6 is controlled by transcriptional and post-transcriptional mechanisms.…”

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confidence: 99%

Interleukin-1 Activates Synthesis of Interleukin-6 by Interfering with a KH-type Splicing Regulatory Protein (KSRP)-dependent Translational Silencing Mechanism

Dhamija

Kuehne

Winzen

et al. 2011

Journal of Biological Chemistry

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Inflammatory gene expression is controlled by post-transcriptional mechanisms. Many relevant transcripts contain AU-rich elements (AREs) 4 that can impose rapid degradation and restrict translation (1-3). Several proteins that interact with and mediate the effects of AREs have been identified. One of them, heterogeneous nuclear ribonucleoprotein K homology (KH)-type splicing regulatory protein (KSRP) is a member of the far upstream sequence element-binding proteins (4). It is a single-stranded nucleic acid-binding protein that contains four KH domains and has been reported to participate in transcription as well as splicing, editing, localization, and degradation of mRNAs and maturation of microRNA precursors (for a review, see Ref. 5). Most recently it has been found to contribute to regulation of RNA 3Ј-end processing (6).KSRP has been shown to facilitate mRNA degradation by directly binding to AREs and recruiting mRNA-degrading enzymes (7,8). Ksrp Ϫ/Ϫ cells and mice produce more type I interferons as a result of decreased mRNA decay and are refractory to viral infection (9). Different conditions of cellular activation or differentiation have been described to reduce KSRP binding and increase stability of specific mRNAs (e.g. Refs. 10 -13). The proinflammatory cytokine IL-1 can induce stabilization of KSRP target mRNAs, including that of IL-6 (14, 15), by reducing interaction of KSRP with the ARE presumably as a result of KSRP phosphorylation by p38 MAP kinase (10).IL-6, originally cloned as 26-kDa protein (16), IFN-␤2 (17), and BSF-2 (18), is a pleiotropic cytokine with important roles in inflammation, immune regulation, oncogenesis, and other physiological and pathological processes. Accordingly, interfering with IL-6 action is the aim of therapeutic strategies (19,20). IL-6 is induced in various cell types by a plethora of activators. Among the strongest and first identified are the proinflammatory cytokines tumor necrosis factor (TNF) (21) and IL-1 (22). Expression of IL-6 is controlled by transcriptional and post-transcriptional mechanisms. The latter involve AREs and a putative stem-loop structure that cause rapid degradation of the mRNA (23). Activators like IL-1 and lipopolysaccharide induce IL-6 mRNA stabilization through p38 MAPK/MK2 signaling (14, 24). IL-6 expression is also controlled by miRNAs (25,26).Our recent data showed that, in addition to stabilizing mRNAs, IL-1 can activate translation of mRNAs, including that of . We now provide evidence that repressed basal translation of IL-6 and a group of other mRNAs depends on KSRP. Interaction of KSRP with the IL-6 ARE is direct and is decreased in response to IL-1, suggesting a novel, miRNA-independent function for KSRP in translation.

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“…Further, the gene coding for the 26-kDa protein is also induced by a highly purified interleukin 1ip (IL-1p3)-related protein obtained from con A-stimulated human leukocytes (5), later demonstrated to be identical to IL-1f3 (6). Although it has been claimed that the 26-kDa protein has a weak IFN-like activity-neutralized by anti-IFN-p8 sera-the biological function of this molecule remained mysterious until the recent report of an identical cDNA sequence coding for an interleukin, active on Blymphocytes (7)(8)(9), and having a potent growth factor activity on the same cells (10).…”

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confidence: 99%

Induction and regulation of mRNA encoding 26-kDa protein in human cell lines treated with recombinant human tumor necrosis factor.

Defilippi¹,

Poupart²,

Tavernier³

et al. 1987

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

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A 26-kDa protein, originally described in human fibroblasts superinduced for interferon f3 (IFN-13) production, and termed IFN-f32 by other investigators, is induced by cycloheximide and by a 22-kDa, interleukin 1 (IL-1)-related factor. Although the structure and sequence of the corresponding gene show nonhomology with the IFN-f3 gene, the gene is identical to that of B-cell stimulatory factor 2, a human interleukin, and displays a very potent growth and differentiation factor activity for B lymphocytes. In this work we show that IL-1,8 and tumor necrosis factor (TNF) strongly induce the 26-kDa protein in FS-4 fibroblasts and in some transformed cell lines. Addition of cycloheximide to recombinant (r)IL-l and rTNF further enhances the level of 26-kDaprotein mRNA. We determined the kinetics of induction and the amounts of rTNF and rIL-1j3 required for optimal induction of this mRNA in FS-4 cells and in HeLa H21 cells and found that rIL-1f3 is a more efficient inducer of 26-kDa protein mRNA than is TNF. By analyzing the inducibility of the 26-kDa protein gene by rTNF and rIL-1/3 in a series of transformed cell lines that differ in their sensitivity to the cytotoxic action of TNF, we report a direct correlation between the 26-kDa protein mRNA expression and the resistance of these cells to the cytotoxic effect of TNF.When human fibroblast cells are induced to produce interferon (IFN)-p by treatment with poly(I)-poly(C) in the presence of cycloheximide (CHX), synthesis of a protein of 26 kDa (1), earlier described as , is stimulated.Induced epithelial cells (3) and peripheral blood lymphocytes (4) also express the 26-kDa-protein mRNA. Further, the gene coding for the 26-kDa protein is also induced by a highly purified interleukin 1ip (IL-1p3)-related protein obtained from con A-stimulated human leukocytes (5), later demonstrated to be identical to . Although it has been claimed that the 26-kDa protein has a weak IFN-like activity-neutralized by anti-IFN-p8 sera-the biological function of this molecule remained mysterious until the recent report of an identical cDNA sequence coding for an interleukin, active on Blymphocytes (7)(8)(9), and having a potent growth factor activity on the same cells (10).Tumor necrosis factor (TNF) is a cytokine secreted by macrophages and/or monocytic cell lines upon stimulatione.g., by lipopolysaccharide (LPS). It was discovered originally in the sera of mice treated with bacillus CalmetteGuerin (BCG), followed by an endotoxin challenge for a few hours, a substance that causes hemorrhagic necrosis, or, in some cases, complete regression of certain transplanted tumors in mice (11). In the last few years human TNF cDNA has been cloned, sequenced, and efficiently expressed in Escherichia coli by several groups (12)(13)(14). The biological activities exerted by TNF are very broad. In vitro recombinant (r)TNF has divergent effects on the cell physiology, being either cytocidal and cytostatic on some transformed cell lines and inactive on others (15), or growth-promoting in normal dip...

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Induction of a 26-kDa-protein mRNA in human cells treated with an interleukin-1-related, leukocyte-derived factor

Cited by 163 publications

References 24 publications

Tumor necrosis factor inhibits collagen and fibronectin synthesis in human dermal fibroblasts

Tumor necrosis factor inhibits collagen and fibronectin synthesis in human dermal fibroblasts

Interleukin-1 Activates Synthesis of Interleukin-6 by Interfering with a KH-type Splicing Regulatory Protein (KSRP)-dependent Translational Silencing Mechanism

Induction and regulation of mRNA encoding 26-kDa protein in human cell lines treated with recombinant human tumor necrosis factor.

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