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001-es BibID:	BIBFORM086503
035-os BibID:	(WoS)000559845300001 (Scopus)85085550676
Első szerző:	Varga Zsófia (molekuláris biológus)
Cím:	Differences in the sensitivity of classically and alternatively activated macrophages to TAK1 inhibitor-induced necroptosis / Zsófia Varga, Tamás Molnár, Anett Mázló, Ramóna Kovács, Viktória Jenei, Krisztina Kerekes, Attila Bácsi, Gábor Koncz
Dátum:	2020
ISSN:	0340-7004
Megjegyzések:	Controlling the balance of pro-inflammatory M1 versus anti-inflammatory M2 macrophages may have paramount therapeutic benefit in cardiovascular diseases, infections, cancer and chronic inflammation. The targeted depletion of different macrophage populations provides a therapeutic option to regulate macrophage-mediated functions. Macrophages are highly sensitive to necroptosis, a newly described regulated cell death mediated by receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain like pseudokinase. Antagonists of inhibitors of apoptosis proteins (SMAC mimetics) block RIPK1 ubiquitination, while TGF-activated kinase 1 (TAK1) inhibitors prevent the phosphorylation of RIPK1, resulting in increased necroptosis. We compared the sensitivity of monocyte-derived human M1 and M2 cells to various apoptotic and necroptotic signals. The two cell types were equally sensitive to all investigated stimuli, but TAK1 inhibitor induced more intense necroptosis in M2 cells. Consequently, the treatment of co-cultured M1 and M2 cells with TAK1 inhibitor shifted the balance of the two populations toward M1 dominance. Blockage of either Aurora Kinase A or glycogen synthase kinase 3 beta, two newly described necroptosis inhibitors, increased the sensitivity of M1 cells to TAK1-inhibitor-induced cell death. Finally, we demonstrated that in vitro differentiated tumor-associated macrophages (TAM-like cells) were as highly sensitive to TAK1 inhibitor-induced necroptosis as M2 cells. Our results indicate that at least two different necroptotic pathways operate in macrophages and the targeted elimination of different macrophage populations by TAK1 inhibitor or SMAC mimetic may provide a therapeutic option to regulate the balance of inflammatory/anti-inflammatory macrophage functions.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Necroptosis Macrophage Infammation Cancer
Megjelenés:	Cancer Immunology Immunotherapy. - 8 (2020), p. 1-15. -
További szerzők:	Molnár Tamás (1989-) (molekuláris biológus) Türk-Mázló Anett (1989-) (molekuláris biológus) Kovács Ramóna (1991-) (biológus, okleveles klinikai laboratóriumi kutató) Jenei Viktória (1997-) (biológus) Kerekes Krisztina Bácsi Attila (1967-) (immunológus) Koncz Gábor (1970-) (biológus, immunológus)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00005 GINOP NKFIH 125224 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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