2026-05-17T05:52:42Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/173722024-09-28T02:18:35Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616
Repisalud
author
Jimenez-Garcia, Lidia
author
Higueras, María Ángeles
author
Herranz, Sandra
author
Hernández-López, Marta
author
Luque, Alfonso
author
de Las Heras, Beatriz
author
Hortelano, Sonsoles
funder
Instituto de Salud Carlos III
funder
Ministerio de Sanidad (España)
2024-01-25T14:56:03Z
2024-01-25T14:56:03Z
2018-08
Biochem Pharmacol. 2018 Aug:154:373-383.
10.1016/j.bcp.2018.06.002
1873-2968
Biochemical pharmacology
29870712
http://hdl.handle.net/20.500.12105/17372
Macrophages are highly plastic cells that adopt different functional phenotypes in response to environmental signals. Classically activated macrophages (M1) exhibit a pro-inflammatory role, mediating host defense against microorganisms or tumor cells; whereas alternatively activated macrophages (M2) perform a range of physiological processes, including inflammation, wound repair and tissue remodeling. Interestingly, M2 macrophages have been involved in pathological settings such as tumor progression, parasitic infection and respiratory disorders. Consequently, the search of new agents able to control macrophage polarization is on the basis of new therapeutic strategies. In the present study, we have evaluated the effect of the hispanolone derivative 8,9-dehydrohispanolone-15,16-lactol (DHHL) on M2 macrophage polarization. Our results reveal that DHHL significantly inhibited IL-4- or IL-13-stimulated M2 macrophage activation, as showed by reduced expression of M2 markers. In addition, DHHL suppressed IL-4-induced STAT-6 and JAK-1 tyrosine phosphorylation, suggesting that this compound inhibited M2 polarization by suppressing the JAK-STAT signaling pathway. Finally, DHHL prevented eosinophil recruitment and the presence of F4/80+-CD206+ M2-like macrophages in an in vivo model of M2 polarization via administration of chitin. Collectively, these results confirm DHHL as a novel regulator of macrophage polarization suitable to design future therapies towards M2-macrophages mediated pathologies.
eng
Chitin
Diterpenoids
Hispanolone
Macrophage polarization
STAT-6
A hispanolone-derived diterpenoid inhibits M2-Macrophage polarization in vitro via JAK/STAT and attenuates chitin induced inflammation in vivo
research article
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Hispanolone-derivedDiterpenoidInhibits_2018.pdf
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Hispanolone-derivedDiterpenoidInhibits_2018.pdf.txt