5‐aminoimidazole‐4‐carboxamide‐1‐beta‐4‐ribofuranoside attenuates experimental autoimmune encephalomyelitis via modulation of endothelial–monocyte interaction

Prasad, Ratna; Giri, Shailendra; Nath, Narender; Singh, Inderjit; Singh, Avtar

doi:10.1002/jnr.20953

Cited by 58 publications

(67 citation statements)

References 55 publications

(73 reference statements)

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“…37 Briefly, female C57BL/6 mice were challenged with a total of 300 g of MOG [38][39][40][41][42][43][44][45][46][47][48][49][50] peptide (divided into two subcutaneous injections, one on each dorsal flank) in 0.1 ml of phosphate-buffered saline (PBS), emulsified in an equal volume of Complete Freund's Adjuvant (CFA) containing 4 mg/ml of Mycobacterium tuberculosis H37RA (Difco, Detroit, MI). These mice were simultaneously injected intravenously with 100 ng of pertussis toxin in 0.2 ml of PBS.…”

Section: Induction and Disease Evaluation Of Eaementioning

confidence: 99%

“…For cytokine assays, splenocytes were cultured at 1.5 ϫ 10 6 cells per well in 0.2 ml of Dulbecco's modified Eagle's medium with 10% fetal bovine serum, in the presence or absence of different concentrations of MOG [38][39][40][41][42][43][44][45][46][47][48][49][50] peptide, or 1 g/ml of Con A (Sigma-Aldrich, St. Louis, MO). Conditioned media were collected 40 hours later, and cytokine concentrations were determined by quantitative ELISA using paired mAb specific for the corresponding cytokines per the manufacturer's recommendations (BD Pharmingen).…”

Section: Cytokine and Proliferation Assaysmentioning

confidence: 99%

“…BBB permeability was assessed essentially as described, 39 with some modifications. Briefly, on days 6 and 13 after MOG challenge, 4% Evans blue dye (SigmaAldrich) was injected into the tail veins of C57BL/6 mice.…”

Section: Measurement Of Blood-brain Barrier (Bbb) Permeabilitymentioning

confidence: 99%

“…To this end, a single encephalitogenic dose of MOG [38][39][40][41][42][43][44][45][46][47][48][49][50] peptide was administered to C57BL/6 mice. Two days after peptide injection, we administered by hydrodynamic injection a single dose of pFn14-TRAIL ⅐ SBC21 plasmid (50 g/ mouse), or one of four control plasmids [pFn14 ⅐ SBC21, pFn14-IgG1(mut) ⅐ SBC21, pTRAIL ⅐ SBC21, and pSBC21].…”

Section: Fn14-trail Suppresses Mog-induced Autoimmune Encephalomyelitismentioning

confidence: 99%

“…This was evaluated in the same EAE model. Two days after administering a single encephalitogenic challenge of MOG [38][39][40][41][42][43][44][45][46][47][48][49][50] peptide to C57BL/6 mice, single doses of either pFn14-TRAIL ⅐ SBC21 plasmid (25 g/mouse) or a mixture of pFn14 ⅐ SBC21 and pTRAIL ⅐ SBC21 plasmids (25 g each/mouse) were hydrodynamically injected into the animals. Although Fn14-TRAIL significantly suppressed EAE as before, with decreases in both mean clinical scores (Figure 4, A and B) and cumulative mean clinical score (Figure 4C), the combination of soluble Fn14 and soluble TRAIL showed no significant therapeutic effect.…”

Section: Fn14-trail Is More Effective Than Its Component Parts In Comentioning

confidence: 99%

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Fn14-TRAIL, a Chimeric Intercellular Signal Exchanger, Attenuates Experimental Autoimmune Encephalomyelitis

Razmara

Hilliard

Ziarani

et al. 2009

The American Journal of Pathology

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Hallmarks of the pathogenesis of autoimmune encephalomyelitis include perivascular infiltration of inflammatory cells into the central nervous system, multifocal demyelination in the brain and spinal cord, and focal neuronal degeneration. Optimal treatment of this complex disease will ultimately call for agents that target the spectrum of underlying pathogenic processes. In the present study, Fn14-TRAIL is introduced as a unique immunotherapeutic fusion protein that is designed to exchange and redirect intercellular signals within inflammatory cell networks, and, in so doing, to impact multiple pathogenic events and yield a net anti-inflammatory effect. In this soluble protein product, a Fn14 receptor component (capable of blocking the pro-inflammatory TWEAK ligand) is fused to a TRAIL ligand (capable of inhibiting activated, pathogenic T cells). Sustained Fn14-TRAIL expression was obtained in vivo using a transposon-based eukaryotic expression vector. Fn14-TRAIL expression effectively prevented chronic, nonremitting, paralytic disease in myelin oligodendrocyte glycoprotein-challenged C57BL/6 mice. Disease suppression in this model was reflected by decreases in the clinical score, disease incidence, nervous tissue inflammation, and Th1, Th2, and Th17 cytokine responses. Significantly, the therapeutic efficacy of Fn14-TRAIL could not be recapitulated simply by administering its component parts (Fn14 and TRAIL) as soluble agents, either alone or in combination. Its functional pleiotropism was manifest in its additional ability to attenuate the enhanced permeability of the blood-brain barrier that typically accompanies autoimmune encephalomyelitis. (Am J Pathol

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Section: Induction and Disease Evaluation Of Eaementioning

confidence: 99%

Section: Cytokine and Proliferation Assaysmentioning

confidence: 99%

Section: Measurement Of Blood-brain Barrier (Bbb) Permeabilitymentioning

confidence: 99%

Section: Fn14-trail Suppresses Mog-induced Autoimmune Encephalomyelitismentioning

confidence: 99%

Section: Fn14-trail Is More Effective Than Its Component Parts In Comentioning

confidence: 99%

See 3 more Smart Citations

Fn14-TRAIL, a Chimeric Intercellular Signal Exchanger, Attenuates Experimental Autoimmune Encephalomyelitis

Razmara

Hilliard

Ziarani

et al. 2009

The American Journal of Pathology

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GSNO attenuates EAE disease by S‐nitrosylation‐mediated modulation of endothelial‐monocyte interactions

Prasad

Giri

Nath

et al. 2006

Glia

Self Cite

106

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S-Nitrosoglutathione (GSNO) is an endogenous nitric oxide carrier and recently, has been documented for its anti-inflammatory effects in rat model of cerebral ischemia (Khan et al. (2005) J Cereb Blood Flow Metab 25:177-192). Here, we explored the neuroprotective effects mediated by GSNO in Lewis rat model of EAE and its mechanism of action using in vitro model of monocyte-endothelial cell interaction. Oral administration of GSNO attenuated the clinical disease course in EAE animals by inhibiting the infiltration of vascular immune cells in the CNS that subsequently led to the reduction in the expression of proinflammatory cytokines and consequently limited demyelination. Based on the inhibition in infiltration of immune cells, we hypothesized that GSNO modulated endothelial cell activation that led to reduce cellular infiltration in the CNS. Using an in vitro model, we established that GSNO inhibited monocyte adhesion to the activated endothelial cell, which was mediated by down regulation of endothelial cell adhesion molecules (CAMs). The mechanism by which GSNO modulated CAMs expression appeared to be via S-nitrosylation of p65, which consequently inhibited nuclear factor kappa B (NF-kappaB) activation in endothelial cells. These observations suggest that GSNO exerts its protective effects in EAE by inhibition of cellular infiltration into the CNS by S-nitrosylation of p65, thereby modulating NF-kappaB-CAMs pathway in endothelial cells.

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Inhibition of lipopolysaccharide‐induced inducible nitric oxide synthase and cyclooxygenase‐2 gene expression by 5‐aminoimidazole‐4‐carboxamide riboside is independent of AMP‐activated protein kinase

Kuo

Chang

et al. 2007

J of Cellular Biochemistry

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Recent studies suggest AMP-activated protein kinase (AMPK), an enzyme involved in energy homeostasis, might be a novel signaling pathway in regulating inflammatory response, but the precise intracellular mechanisms are not fully understood. In this study, we have demonstrated that 5-aminoimidazole-4-carboxamide riboside (AICAR), an activator of AMPK, inhibited lipopolysaccharide (LPS)-induced protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in macrophages and microglial cells at the gene transcription level. Data obtained from electrophoretic mobility shift assay (EMSA) and promoter activity assay have further confirmed the ability of AICAR to block LPS-mediated NF-kappaB, AP-1, CREB, and C/EBPbeta activation. However, AICAR did not affect LPS-mediated IKK, ERK, and p38 activation. Regardless of the ability of AICAR to activate AMPK, the inhibitory effects of AICAR on iNOS and COX-2 expression were not associated with AMPK. An adenosine kinase inhibitor 5'-iodotubercidin, which effectively abolished AMPK activation caused by AICAR, did not reverse the anti-inflammatory effect of AICAR. Moreover, another AMPK activator metformin was not able to mimic the effects of AICAR. Direct addition of AICAR in EMSA assay interrupted binding of NF-kappaB, CREB, and C/EBPbeta to specific DNA elements. Taken together, this study demonstrates that the anti-inflammatory effects of AICAR against LPS-induced iNOS and COX-2 gene transcription are not associated with AMPK activation, but might be resulting from the direct interference with DNA binding to transcription factors.

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5‐aminoimidazole‐4‐carboxamide‐1‐beta‐4‐ribofuranoside attenuates experimental autoimmune encephalomyelitis via modulation of endothelial–monocyte interaction

Cited by 58 publications

References 55 publications

Fn14-TRAIL, a Chimeric Intercellular Signal Exchanger, Attenuates Experimental Autoimmune Encephalomyelitis

Fn14-TRAIL, a Chimeric Intercellular Signal Exchanger, Attenuates Experimental Autoimmune Encephalomyelitis

GSNO attenuates EAE disease by S‐nitrosylation‐mediated modulation of endothelial‐monocyte interactions

Inhibition of lipopolysaccharide‐induced inducible nitric oxide synthase and cyclooxygenase‐2 gene expression by 5‐aminoimidazole‐4‐carboxamide riboside is independent of AMP‐activated protein kinase

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