Monocytes Stimulated by 110-kDa Fibronectin Fragments Suppress Proliferation of Anti-CD3-Activated T Cells

Birdsall, Holly H.; Porter, Wendy J.; Trial, JoAnn; Rossen, Roger D.

doi:10.4049/jimmunol.175.5.3347

Cited by 12 publications

(16 citation statements)

References 28 publications

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“…Previous studies that attempted to elucidate the in vitro effect of FN fragments on cell behavior used one isolated FN fragment, which was obtained commercially, often originating from the N terminus of the molecule [29,37,38]. However, such an approach does not take into consideration the fact that monocytes respond to the integrated sum of all signals provided by the mixture of different FN fragments.…”

Section: Discussionmentioning

confidence: 98%

Native and fragmented fibronectin oppositely modulate monocyte secretion of MMP-9

Marom

Rahat²,

Lahat³

et al. 2007

Journal of Leukocyte Biology

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Monocytes remodel the extracellular matrix (ECM) by secreting proteins composing the ECM such as fibronectin (FN) and degrading proteases such as matrix metalloproteinase-9 (MMP-9), which cleaves FN into fragments. The effects of FN and its fragmented products on the expression of monocyte MMP-9 are controversial and largely unknown. We showed that in human monocytes, the proinflammatory cytokine TNF-alpha induced MMP-9 secretion and increased fragmentation of FN into distinct fragments. When primary monocytes or the U937 monocytic cell line were incubated on a plastic substrate, plastic-coated with native FN, and plastic-coated with fragmented FN (frag-FN), native FN inhibited TNF-alpha-induced proMMP-9 secretion by twofold (P<0.01) compared with plastic or frag-FN. Exploration of the dynamics of inflammation by incubating cells sequentially on the three substrates showed that frag-FN opposed the inhibitory effect of native FN. Inhibition of proMMP-9 by native FN was exerted at the translational level, as no change in MMP-9 mRNA, intracellular protein accumulation, or proteomic degradation was observed, and when degradation was blocked, no de novo translation of MMP-9 could be measured. We also showed that the reduction of MMP-9 secretion by native FN was responsible for attenuated migration of U937 cells (P<0.05). We suggest that in the inflammatory tissue, intact, native FN has a homeostatic role in harnessing MMP-9 activity. However, as fragmented products accumulate locally, they alleviate the inhibition and enable faster migration of the monocytes through the degraded ECM.

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Section: Discussionmentioning

confidence: 98%

Native and fragmented fibronectin oppositely modulate monocyte secretion of MMP-9

Marom

Rahat²,

Lahat³

et al. 2007

Journal of Leukocyte Biology

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“…In our system, CD4 + Th cells were activated with the platebound anti-CD3 mAb, because anti-CD3 mAb can react with the TCR-CD3 complex and initiate the intracellular biochemical pathway resulting in cellular activation and proliferation and it has been used extensively as a polyclonal activator of T cells in vitro [46][47][48].…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoids impair microglia ability to induce T cell proliferation and Th1 polarization

Li¹,

Wang²,

Guo³

et al. 2007

Immunology Letters

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“…They typically have less affinity for GC-oligonucleotide (1, 3, 6) or none at all (2). For 4 and 5, which showed no affinity for AT, formation of ligand-GC complexes is also improbable.…”

Section: Molecular Docking Of Compounds In Sg Of Oligonucleotidesmentioning

confidence: 95%

“…Protoberberine compounds include an important class of isoquinoline alkaloids (IQA) that exhibit a broad spectrum of pharmacological activity [1,2]. The type of IQA is currently of great interest because of the characteristic manifestation of high cytotoxicity and antiparasite activity (for example, berberine is known in folk medicine as a powerful agent for treating many parasite-borne diseases) [3].…”

mentioning

confidence: 99%

Antiparasitic activity of certain isoquinoline alkaloids and their hypothetical complexes with oligonucleotides

et al. 2008

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The antiparasitic activity of two tetrahydrodiisoquinoline alkaloids 2, 3, β-allocryptopine (4), protopine (5), and a substituted phenylethylamine 6 was studied. Compounds 2 and 6 inhibited the growth of the parasite Leishmania donovani. The capability of the examined compounds to bind DNA was estimated by molecular modeling. It has been shown that binding occurs in the small groove and primarily at the AT-enriched part of the oligonucleotide.Protoberberine compounds include an important class of isoquinoline alkaloids (IQA) that exhibit a broad spectrum of pharmacological activity [1,2]. The type of IQA is currently of great interest because of the characteristic manifestation of high cytotoxicity and antiparasite activity (for example, berberine is known in folk medicine as a powerful agent for treating many parasite-borne diseases) [3]. Considering the demand for new promising antiparasite and antitumor preparations [4,5], the present work is very timely.The antitumor activity of berberine (1) and its cytotoxic analogs is related to their ability to inactivate topoisomerase I (and topoisomerase II in certain instances). It is assumed that the key step in this process is the specific binding of the alkaloid to DNA that stabilizes the ternary complex DNA-topoisomerase-alkaloid [6][7][8]. Under normal conditions (without alkaloid), topoisomerase I performs one of its key tasks related to the cleavage of two DNA chains (introduces a single-strand break into the DNA chain), thereby preparing for the subsequent processes of replication and transcription. Fluorescence analysis and NMR spectroscopy have now established that berberine exhibits high affinity toward DNA [9]. Studies of the interaction of protoberberine alkaloids with oligonucleotides confirm the hypothesis that the alkaloid binds primarily to the small groove (SG) of the DNA helix [7,9,10].The mechanism of the antiparasite activity of berberine and its analogs cannot be unambiguously determined by experimental data. In particular, it cannot be determined if this is a consequence of binding with kinetoplast DNA. However, it has been reported that compounds that are cytotoxic or have the capability to interact with human DNA typically exhibit antiparasite activity. The interaction with the SG or intercalation are usually examined because both of these types of interaction affect DNA and/or topoisomerase of parasites [11][12][13]. The alkaloid camptothecine, on the basis of which many antitumor preparations have been created and tested clinically, provides an example. Camptothecine, like berberine, forms ternary complexes with DNA and topoisomerase. it has been shown experimentally that camptothecine can form covalent DNA-topoisomerase complexes with human (nuclear) DNA and kinetoplast DNA isolated from trypanosomes, leischmania, and other parasites [6].

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Monocytes Stimulated by 110-kDa Fibronectin Fragments Suppress Proliferation of Anti-CD3-Activated T Cells

Cited by 12 publications

References 28 publications

Native and fragmented fibronectin oppositely modulate monocyte secretion of MMP-9

Native and fragmented fibronectin oppositely modulate monocyte secretion of MMP-9

Glucocorticoids impair microglia ability to induce T cell proliferation and Th1 polarization

Antiparasitic activity of certain isoquinoline alkaloids and their hypothetical complexes with oligonucleotides

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