Cromolyn inhibits the secretion of inflammatory cytokines by human microglia (HMC3)

Abstract Cromolyn is a known mast cell stabilizer and is approved for treatment of asthma and for other allergic indications. Cromolyn, in a new redesigned dry powder formulation, is being tested in a pivotal clinical trial in combination with low dose ibuprofen to treat early Alzheimer’s Disease (A...

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Autores principales:	Yi-Jun Wang, Alina Monteagudo, Matthew A. Downey, Philip G. Ashton-Rickardt, David R. Elmaleh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/12e89e9db6224c8982a7700a49b3f833
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spelling	oai:doaj.org-article:12e89e9db6224c8982a7700a49b3f8332021-12-02T18:03:32ZCromolyn inhibits the secretion of inflammatory cytokines by human microglia (HMC3)10.1038/s41598-021-85702-82045-2322https://doaj.org/article/12e89e9db6224c8982a7700a49b3f8332021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85702-8https://doaj.org/toc/2045-2322Abstract Cromolyn is a known mast cell stabilizer and is approved for treatment of asthma and for other allergic indications. Cromolyn, in a new redesigned dry powder formulation, is being tested in a pivotal clinical trial in combination with low dose ibuprofen to treat early Alzheimer’s Disease (AD) subjects. To better understand the mechanistic effect cromolyn has in slowing down or halting the neuroinflammatory response associated with AD progression, we tested the effect of cromolyn to dampen the inflammatory response in the human HMC3 microglia cell line. The direct effect of cromolyn on HMC3 microglia is on cytokines and chemokines production following their activation by the inflammatory cytokine TNF-α. Cromolyn and a new fluorinated analog dramatically reduced the secretion of a wide spectrum of inflammatory mediators, which included cytokines such as IL-1β, IL-6, IL-8 and IFN-γ, and chemokines such as CXCL10, CCL2, CCL3 and CCL4. These results bolster our understanding of how our cromolyn platform modulates toxic microglia behavior as a dynamic future treatment option for neurodegenerative disorders.Yi-Jun WangAlina MonteagudoMatthew A. DowneyPhilip G. Ashton-RickardtDavid R. ElmalehNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yi-Jun Wang Alina Monteagudo Matthew A. Downey Philip G. Ashton-Rickardt David R. Elmaleh Cromolyn inhibits the secretion of inflammatory cytokines by human microglia (HMC3)
description	Abstract Cromolyn is a known mast cell stabilizer and is approved for treatment of asthma and for other allergic indications. Cromolyn, in a new redesigned dry powder formulation, is being tested in a pivotal clinical trial in combination with low dose ibuprofen to treat early Alzheimer’s Disease (AD) subjects. To better understand the mechanistic effect cromolyn has in slowing down or halting the neuroinflammatory response associated with AD progression, we tested the effect of cromolyn to dampen the inflammatory response in the human HMC3 microglia cell line. The direct effect of cromolyn on HMC3 microglia is on cytokines and chemokines production following their activation by the inflammatory cytokine TNF-α. Cromolyn and a new fluorinated analog dramatically reduced the secretion of a wide spectrum of inflammatory mediators, which included cytokines such as IL-1β, IL-6, IL-8 and IFN-γ, and chemokines such as CXCL10, CCL2, CCL3 and CCL4. These results bolster our understanding of how our cromolyn platform modulates toxic microglia behavior as a dynamic future treatment option for neurodegenerative disorders.
format	article
author	Yi-Jun Wang Alina Monteagudo Matthew A. Downey Philip G. Ashton-Rickardt David R. Elmaleh
author_facet	Yi-Jun Wang Alina Monteagudo Matthew A. Downey Philip G. Ashton-Rickardt David R. Elmaleh
author_sort	Yi-Jun Wang
title	Cromolyn inhibits the secretion of inflammatory cytokines by human microglia (HMC3)
title_short	Cromolyn inhibits the secretion of inflammatory cytokines by human microglia (HMC3)
title_full	Cromolyn inhibits the secretion of inflammatory cytokines by human microglia (HMC3)
title_fullStr	Cromolyn inhibits the secretion of inflammatory cytokines by human microglia (HMC3)
title_full_unstemmed	Cromolyn inhibits the secretion of inflammatory cytokines by human microglia (HMC3)
title_sort	cromolyn inhibits the secretion of inflammatory cytokines by human microglia (hmc3)
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/12e89e9db6224c8982a7700a49b3f833
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_version_	1718378673207246848

Cromolyn inhibits the secretion of inflammatory cytokines by human microglia (HMC3)

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