A new ditriazine inhibitor of NF-κB modulates chronic inflammation and angiogenesis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-05

AUTHORS

Inmaculada Rioja, Carmen M. Terencio, Amalia Ubeda, Ricardo Riguera, José M. Quintela, José M. Alcaraz

ABSTRACT

We have previously shown that a ditriazine derivative 4,10-dichloropyrido[5,6:4,5]thieno[3,2- d':3,2- d]-1, 2, 3-ditriazine (DTD) modulates acute inflammation in murine models by inhibition of leukocyte functions and expression of inducible enzymes including nitric oxide synthase and cyclooxygenase-2 (COX-2). In the present work, we have demonstrated the anti-inflammatory effect of DTD after oral administration in the rat adjuvant-induced arthritis, by reduction of interleukin-1beta and tumour necrosis factor-alpha levels and COX-2 expression in the inflamed tissues. These mediators were also significantly decreased by DTD treatment in the angiogenesis-dependent murine air pouch granuloma model, where this agent exerted anti-inflammatory and antiangiogenic effects. In vitro experiments indicated that DTD is an inhibitor of the nuclear factor-kappaB (NF-kappaB) pathway of cellular activation in macrophages, in parallel with the regulation of cytokine release. Our results suggest that the anti-inflammatory and antiangiogenic properties of DTD can be related to the inhibition of cytokine and PGE(2) production by interfering with NF-kappaB activation. This compound thus offers a therapeutic potential for the treatment of chronic inflammatory diseases with an angiogenic component, such as rheumatoid arthritis. More... »

PAGES

357-364

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00210-002-0544-z

DOI

http://dx.doi.org/10.1007/s00210-002-0544-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1024304162

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12012021


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