Anti-Inflammatory Drug Effects on Apoptosis of Eosinophil Granulocytes Derived from Murine Bone-Marrow: Cellular Mechanisms as Related to Lineage, Developmental Stage and Hemopoietic Environment

ISSN: 1875-614X (Online)
ISSN: 1871-5230 (Print)


Volume 15, 3 Issues, 2016


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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents

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Editor-in-Chief:
Claudiu T. Supuran
Neurofarba Department
University of Florence
Florence
Italy


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Anti-Inflammatory Drug Effects on Apoptosis of Eosinophil Granulocytes Derived from Murine Bone-Marrow: Cellular Mechanisms as Related to Lineage, Developmental Stage and Hemopoietic Environment



Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 5(1): 13-25.

Author(s): Maria I. C. G. Elsas and P X Elsas.

Affiliation: Dept. of Pediatrics, Instituto Fernandes Figueira, FIOCRUZ, Brazil.

Abstract

The effects of a variety of widely used anti-inflammatory agents (dexamethasone, indomethacin, and montelukast) as well as ubiquitous mediators of inflammation (prostaglandin E2 and nitric oxide) on the development of murine eosinophils ex vivo and in vivo have been studied over the last decade. The results indicate that developing eosinophils differ markedly in their responses to these agents from the mature forms of the same lineage, studied either in allergic human subjects or experimental animal models of allergic disease. Most strikingly, glucocorticoids strongly enhance eosinophil development, both in vitro and in vivo. The enhancing effects are also observed during stress reactions and are strictly dependent on stress-induced glucocorticoid hormone production from the adrenal glands. Some, but not all, of the developmental effects of glucocorticoids on eosinophils could be accounted for their ability to prevent generation of nitric oxide through inducible NO synthase, which leads to apoptosis through the CD95-CD95L pathway. A novel mechanism for the effects of indomethacin in upregulating the development of eosinophils has also been documented. Evidence that lineage-specific as well as stage-specific cellular response programmes determine these different outcomes is discussed, along with the perspectives for future research.

Keywords:

inflammation, eosinophilia, Glucocorticoids, rolipram, cyclooxygenases, eosinophil peroxidase-positive.



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Article Details

Volume: 5
Issue Number: 1
First Page: 13
Last Page: 25
Page Count: 13
DOI: 10.2174/187152306775537274
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