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Updated: Aug 20, 2025
An In vitro Model to Study Heterogeneity of Human Macrophage Differentiation and Polarization
Published on: June 12, 2013
Pan HDACi Valproic Acid and Trichostatin A Show Apparently Contrasting Inflammatory Responses in Cultured J774A.1
Ubah Dominic Babah Ubah1, Korawin Triyasakorn1, Brandon Roan2
1Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, Idaho State University, 921 S 8th Avenue, Mail Stop 8288, Pocatello, ID 83209, USA.
Abstract:
This study was initiated as an attempt to clarify some of the apparent conflicting data regarding the so-called anti-inflammatory versus proinflammatory properties of histone deacetylase inhibitors (HDACis). In cell culture, typically, chronic pretreatment with the HDACi valproic acid (VPA) and trichostatin A (TSA) exhibits an anti-inflammatory effect. However, the effect of acute treatment with VPA and TSA on the levels of inflammatory cytokines in J774A.1 macrophage cell line is unknown. Therefore, this study investigated the effect of acute treatment with VPA and TSA on levels of key inflammatory cytokines in maximally stimulated J774A.1 cells. J774A.1 macrophages were treated with either VPA or TSA for 1 h (acute treatment), followed by maximal stimulation with LPS + IFNγ for 24 h. ELISA was used to measure the levels of proinflammatory cytokines TNFα, NO and IL-1β from the culture medium. Acute treatment with VPA showed a dose-dependent increase in levels of all three cytokines. Similar to VPA, TSA also showed a dose-dependent increase in levels of IL-1β alone. This study sheds new light on the conflicting data in the literature that may partly be explained by acute or short-term exposure versus chronic or long-term exposure to HDACi.
