Structural and functional comparison of MIF ortholog from Plasmodium yoelii with MIF from its rodent host

Shao, Dingding; Zhong, Xiang; Zhou, Yanfeng; Han, Zhifu; Lin, Ya-Hui; Wang, Zhensheng; Bu, Lingyi; Zhang, Lian-Hui; Su, Xiao‐Dong; Wang, Heng

doi:10.1016/j.molimm.2009.10.037

Cited by 19 publications

(47 citation statements)

References 32 publications

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“…The complete coding region of pymif was PCR amplified from cDNA clone MS36, obtained from a sequenced P. yoelii 17XL blood-stage cDNA library (15,23), using forward primer 5Ј-GATATCATA TGATGCCTTGCTGCGAATTAATAACAAAC-3Ј and reverse primer 5Ј-GAAT TCTCGAGTTAGCCAAATAGTGAACCACTAAAA-3Ј (NdeI and XhoI restriction sites used for subcloning into the pET-30a plasmid [Novagen, Madison, WI] are underlined). The sequence of the pymif cDNA insert was confirmed and shown to be identical to the deposited GenBank sequence under accession number DQ494171 (52).…”

Section: Methodsmentioning

confidence: 81%

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Elevated Levels of thePlasmodium yoeliiHomologue of Macrophage Migration Inhibitory Factor Attenuate Blood-Stage Malaria

et al. 2010

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The excessive production of proinflammatory cytokines plays a significant role in the pathogenesis of severe malaria. Mammalian macrophage migration inhibitory factor (MIF) (mMIF) is an immune mediator that promotes a sustained proinflammatory response by inhibiting the glucocorticoid-mediated downregulation of inflammation. In addition, Plasmodium parasites also encode a homologue of mammalian MIF that is expressed in asexual-stage parasites. We used the Plasmodium yoelii murine model to study the potential role of parasite-encoded MIF in the pathogenesis of malaria. Antibodies raised against purified, non-epitope-tagged P. yoelii MIF (PyMIF) were used to localize expression in trophozoite-and schizont-stage parasites and demonstrate extracellular release. In vitro, recombinant PyMIF was shown to actively induce the chemotaxis of macrophages but did not induce or enhance tumor necrosis factor alpha (TNF-␣) production from peritoneal macrophages. To examine the role of parasite-derived PyMIF in vivo, two transgenic parasite lines that constitutively overexpress PyMIF were generated, one in a nonlethal P. yoelii 17X background [Py17X-MIF(؉)] and the other in a lethal P. yoelii 17XL background [Py17XL-MIF(؉)]. Challenge studies with transgenic parasites in mice showed that the increased expression of PyMIF resulted in a reduction in disease severity. Mice infected with Py17X-MIF(؉) developed lower peak parasitemia levels than controls, while malariaassociated anemia was unaltered. Infection with Py17XL-MIF(؉) resulted in a prolonged course of infection and a reduction in the overall mortality rate. Combined, the data indicate that parasite-derived MIF does not contribute significantly to immunopathology but, through its chemotactic ability toward macrophages, may attenuate disease and prolong infection of highly virulent parasite isolates.

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Section: Methodsmentioning

confidence: 81%

“…Studies of P. berghei-, P. falciparum-, and P. yoelii-encoded MIF revealed a 116-amino-acid protein with ϳ30% amino acid sequence identity with mMIF (2,22,24,52). Collectively, the data suggest that plasmodial MIF (pMIF) is structurally similar to mMIF and possesses some but probably not all activities normally attributed to mMIF.…”

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confidence: 90%

Elevated Levels of thePlasmodium yoeliiHomologue of Macrophage Migration Inhibitory Factor Attenuate Blood-Stage Malaria

et al. 2010

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“…The tautomerase activity of MIFs was also regained by diluting the inactivated MIFs 10-fold, which further proved its reversible nature of inhibition. This non-competitive reversible binding of epoxyazadiradione with MIFs makes it a favorable candidate molecule against the MIF-induced proinflammatory diseases because the other well known MIF inhibitor, ISO-1, is a covalent inhibitor and inhibits huMIF but fails to inhibit MIF activity of parasitic origin (5,19,29). In contrast, epoxyazadiradione inhibits tautomerase activity of MIF of both plasmodial and human origin.…”

Section: Discussionmentioning

confidence: 99%

“…The MIF ortholog from malaria parasite Plasmodium yoelii (PyMIF) has also been reported to induce inflammatory cytokines such as IL-6, IL-10, IFN-␥, TNF-␣, and macrophage chemotactic protein-1 (MCP-1) in BALB/c mice (5). Along with the cytokine activities, MIF also exhibits two distinct catalytic activities, i.e.…”

Section: Macrophage Migration Inhibitory Factor (Mif)mentioning

confidence: 99%

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Novel Anti-inflammatory Activity of Epoxyazadiradione against Macrophage Migration Inhibitory Factor

Alam

Haldar

Thulasiram

et al. 2012

Journal of Biological Chemistry

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Background: Macrophage migration inhibitory factor (MIF) is responsible for proinflammatory reactions in many infectious and non-infectious diseases. Results: Epoxyazadiradione, a limonoid, inhibits the tautomerase activity of both human and malarial MIF and prevents MIF-induced proinflammatory reactions. Conclusion: Epoxyazadiradione bears therapeutic potential against MIF-induced proinflammatory reactions. Significance: This novel molecule is a significant addition in the discovery of anti-inflammatory drugs.

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Parasite MIF Orthologs

Holowka

Bucala

2017

MIF Family Cytokines in Innate Immunity and Homeostasis

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Structural and functional comparison of MIF ortholog from Plasmodium yoelii with MIF from its rodent host

Cited by 19 publications

References 32 publications

Elevated Levels of thePlasmodium yoeliiHomologue of Macrophage Migration Inhibitory Factor Attenuate Blood-Stage Malaria

Elevated Levels of thePlasmodium yoeliiHomologue of Macrophage Migration Inhibitory Factor Attenuate Blood-Stage Malaria

Novel Anti-inflammatory Activity of Epoxyazadiradione against Macrophage Migration Inhibitory Factor

Parasite MIF Orthologs

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