Proinflammatory functions of vascular endothelial growth factor in alloimmunity

Reinders, Marlies E.J.; Sho, Masayuki; Izawa, Atsushi; Wang, Ping; Mukhopadhyay, Debabrata; Koss, Kerith E.; Geehan, Christopher; Luster, Andrew D.; Sayegh, Mohamed H.; Briscoe, David M.

doi:10.1172/jci17712

Cited by 207 publications

(146 citation statements)

References 53 publications

(36 reference statements)

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“…The donor organ is attached via cuffs to the recipient's bronchial and vascular systems permitting normal function. Nonimmunosuppressed recipients experience profound acute rejection within several days largely mediated by IFN-γ and CXCL-10 upregulation [20]–[24]. Over several weeks, chronic rejection occurs with alveolar, pleural, and peribronchial collagen deposition, loss of viable pneumocytes and eventual organ loss.…”

Section: Resultsmentioning

confidence: 99%

Pin1 Modulates the Type 1 Immune Response

et al. 2007

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Background/AbstractImmune responses initiated by T cell receptor (TCR) and costimulatory molecule mediated signaling culminate in maximal cytokine mRNA production and stability. The transcriptional responses to co-stimulatory T cell signalling involve calcineurin and NF-AT, which can be antagonized by interference with the cis-trans peptidyl-prolyl isomerases (PPIase), cyclophilin A and FKBP. Signalling molecules downstream of CD28 which are essential for the stabilization of cytokine mRNAs are largely unknown.Methodology/Principal FindingsWe now show that Pin1, a third member of the PPIase family mediates the post-transcriptional regulation of Th1 cytokines by activated T cells. Blockade of Pin1 by pharmacologic or genetic means greatly attenuated IFN-γ, IL-2 and CXCL-10 mRNA stability, accumulation and protein expression after cell activation. In vivo, Pin1 blockade prevented both the acute and chronic rejection of MHC mismatched, orthotopic rat lung transplants by reducing the expression of IFN-γ and CXCL-10. Combined transcriptional and post-transcriptional blockade with cyclosporine A and the Pin1 inhibitor, juglone, was synergistic.Conclusions/SignificanceThese data suggest Pin1 inhibitors should be explored for use as immunosuppressants and employed with available calcineurin inhibitors to reduce toxicity and enhance effectiveness.

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Section: Resultsmentioning

confidence: 99%

Pin1 Modulates the Type 1 Immune Response

et al. 2007

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“…Human monocytes migrate across collagen membranes and endothelial cell monolayers in response to VEGF, 16 and VEGF induces human T cell migration into skin allografts in the humanised SCID mouse. 17 In addition, VEGF promotes vascular dilatation and increases vascular permeability. 18 19 Inflammatory cell infiltrates and dilated vascular channels were typical in our patients.…”

Section: Discussionmentioning

confidence: 99%

Expression of vascular endothelial growth factor and its receptors in rosacea

Smith

Lanier

Braziel

et al. 2007

British Journal of Ophthalmology

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“…The highlights of this article are as follows: (1) specific and systematical study on the evaluation of the drug targeting effects of the magnetic microspheres both in vitro and in vivo as described above; (2) biodistribution on rats not only in the major tissues (heart, liver, spleen, lung, kidney, and brain) and plasma, but also in lymph nodes; (3) histological study on evaluating the targeting efficiency. Histological studies are usually considered to be a reliable method to detect structural changes due to toxicities (Reinders et al, 2003). Due to the special properties of the magnetic microspheres, it turned to be a method for observing the microspheres' targeting behaviors in tissues in this research.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo evaluation of targeting efficiency of Adriamycin hydrochloride magnetic microspheres

Peng

Yang

et al. 2010

Drug Delivery

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The objective of this study was to prepare magnetic microspheres as a targeting drug delivery system and to specifically evaluate its targeting efficiency. The magnetic microspheres were prepared by emulsion cross-linking techniques. Targeting efficiency was specifically investigated by experiments of biodistribution on rats and histological study. Adriamycin hydrochloride (ADR)-loaded magnetic microspheres were successfully prepared with the mean diameter of 3.853 μm (± 1.484 μm), and had its speciality of superparamagnetism. The results of the targeting efficiency study showed that application of the external magnetic field significantly increased the ADR concentration from 40.28 μg/ml to 100.70 μg/ml at 10 min, 36.99 μg/ml to 91.16 μg/ml at 60 min, and 13.71 μg/ml to 28.30 μg/ml at 180 min in liver as the targeting tissue. The relative uptake efficiencies in liver by injection treatment of ADR magnetic microspheres with external magnetic field were 3.87, 5.59, and 3.34 at 10 min, 60 min, and 180 min after administration, respectively. In conclusion, distinguished targeting efficiency was displayed, which indicated that the magnetic microspheres could be applied as a novel targeting drug delivery system.

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Proinflammatory functions of vascular endothelial growth factor in alloimmunity

Cited by 207 publications

References 53 publications

Pin1 Modulates the Type 1 Immune Response

Pin1 Modulates the Type 1 Immune Response

Expression of vascular endothelial growth factor and its receptors in rosacea

In vitro and in vivo evaluation of targeting efficiency of Adriamycin hydrochloride magnetic microspheres

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