A fluorinated analog of ISO-1 blocks the recognition and biological function of MIF and is orally efficacious in a murine model of colitis

Dagia, Nilesh M.; Kamath, Divya; Bhatt, Pooja; Gupte, Ravindra D.; Dadarkar, Shruta S.; Fonseca, Lyle C.; Agarwal, Gautam; Chetrapal-Kunwar, Anshu; Balachandran, Sarala; Srinivasan, Shaila; Bose, Julie; Pari, Koteppa; B-Rao, Chandrika; Parkale, Santosh S.; Gadekar, Pradip K.; Rodge, Atish H.; Mandrekar, Noopur; Vishwakarma, Ram A.; Sharma, Somesh

doi:10.1016/j.ejphar.2009.02.031

Cited by 33 publications

(33 citation statements)

References 37 publications

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“…Inhibition of the tautomerase activity of MIF reduces inflammation induced by MIF (70,71). Therefore, inhibition of the tautomerase activity of MIFs could inhibit the recruitment of leukocytes and consequently inflammation.…”

Section: Purification Of Epoxyazadiradione and Othermentioning

confidence: 99%

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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Section: Purification Of Epoxyazadiradione and Othermentioning

confidence: 99%

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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“…A volume of 1 ml MIF (recombinant human protein; 30 ng; Piramal Life Sciences) or vehicle (PBS) was microinjected. The endotoxin content in recombinant MIF was negligible (0.15 EU/30 ng purified human MIF) (38). Mice were sutured and monitored during the recovery phase.…”

Section: Intraspinal Stereotaxic Microinjectionsmentioning

confidence: 99%

Macrophage Migration Inhibitory Factor Potentiates Autoimmune-Mediated Neuroinflammation

Cox

Kithcart

Pitt

et al. 2013

The Journal of Immunology

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Macrophage migration inhibitory factor (MIF) is a multipotent cytokine that is associated with clinical worsening and relapses in multiple sclerosis (MS) patients. The mechanism through which MIF promotes MS progression remains undefined. In this study, we identify a critical role for MIF in regulating CNS effector mechanisms necessary for the development of inflammatory pathology in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Despite the ability to generate pathogenic myelin-specific immune responses peripherally, MIF-deficient mice have reduced EAE severity and exhibit less CNS inflammatory pathology, with a greater percentage of resting microglia and fewer infiltrating inflammatory macrophages. We demonstrate that MIF is essential for promoting microglial activation and production of the innate soluble mediators IL-1β, IL-6, TNF-α, and inducible NO synthase. We propose a novel role for MIF in inducing microglial C/EBP-β, a transcription factor shown to regulate myeloid cell function and play an important role in neuroinflammation. Intraspinal stereotaxic microinjection of MIF resulted in upregulation of inflammatory mediators in microglia, which was sufficient to restore EAE-mediated inflammatory pathology in MIF-deficient mice. To further implicate a role for MIF, we show that MIF is highly expressed in human active MS lesions. Thus, these results illustrate the ability of MIF to influence the CNS cellular and molecular inflammatory milieu during EAE and point to the therapeutic potential of targeting MIF in MS.

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“…The above, combined with the observation that an oral dose of 10 mg/kg PIK-75 blunts in vivo-induced production of TNF-␣ and IL-6 by Ͼ50%, but Ͻ100% (see RESULTS section), led us to investigate the effect of PIK-75 in experimental colitis at an oral dose of 10 mg/kg. Colitis was induced in mice by giving 3% (wt/vol) dextran sulfate sodium (DSS; molecular mass 30 -40 kDa; ICN Biomedicals, Aurora, OH) in drinking water ad libitum, as described previously (6,15). DSS-induced colitis was assessed by macroscopic and histological analyses of the colon, as described previously (6,15).…”

Section: Monocyte Endothelial Cell Adhesion Assaymentioning

confidence: 99%

“…Human monocytic THP-1 cells (ATCC, Manassas, VA) were cultured as described previously (15). Phorbol 12-myristate 13-acetate (PMA) differentiation of THP-1 cells was carried out before they were used for experiments.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Human peripheral blood mononuclear cells (hPBMC) were harvested using FicollHypaque density gradient centrifugation (1.077 g/ml; Sigma Aldrich, St. Louis, MO) (6,13,15) and suspended in assay medium (RPMI 1640 culture medium; Sigma Aldrich) containing 10% heat-inactivated fetal bovine serum (JRH), 100 U/ml penicillin (Sigma Chemical), and 100 g/ml streptomycin (Sigma Chemical). Monocytes in the hPBMCs were counted using a Coulter counter, following which the cells were resuspended at 2 ϫ 10 5 monocytes/ml of assay medium.…”

Section: Human Monocyte Assaymentioning

confidence: 99%

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A preferential p110α/γ PI3K inhibitor attenuates experimental inflammation by suppressing the production of proinflammatory mediators in a NF-κB-dependent manner

Dagia¹,

Agarwal²,

Kamath³

et al. 2010

American Journal of Physiology-Cell Physiology

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A fluorinated analog of ISO-1 blocks the recognition and biological function of MIF and is orally efficacious in a murine model of colitis

Cited by 33 publications

References 37 publications

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

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

Macrophage Migration Inhibitory Factor Potentiates Autoimmune-Mediated Neuroinflammation

A preferential p110α/γ PI3K inhibitor attenuates experimental inflammation by suppressing the production of proinflammatory mediators in a NF-κB-dependent manner

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