Valproic acid promotes a decrease in mycobacterial survival by enhancing nitric oxide production in macrophages stimulated with IFN-γ

Nieto-Patlán, Erik; Serafín‐López, Jeanet; Wong‐Baeza, Isabel; Pérez‐Tapia, Sonia Mayra; Cobos-Marín, Laura; Estrada‐Parra, Sergio; Estrada-Garcı́a, Iris; Chávez‐Blanco, Alma; Chacón‐Salinas, Rommel

doi:10.1016/j.tube.2018.12.007

Cited by 19 publications

(14 citation statements)

References 16 publications

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“…Whether this function is affected by VPA needs to be analyzed. Previous reports indicated that VPA can alter the response of macrophages to bacterial pathogens 10,40 . TLRs plays a crucial role in sensing of different bacteria, and interestingly PLCγ2 regulates the signaling of TLR‐4, 41 suggesting a possible effect of VPA in TLR activation pathway.…”

Section: Resultsmentioning

confidence: 96%

The histone deacetylase inhibitor valproic acid attenuates phospholipase Cγ2 and IgE-mediated mast cell activation

Rodríguez-López

Soria-Castro

Campillo-Navarro

et al. 2020

Journal of Leukocyte Biology

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Mast cell activation through the high‐affinity IgE receptor (FcεRI) plays a central role in allergic reactions. FcεRI‐mediated activation triggers multiple signaling pathways leading to degranulation and synthesis of different inflammatory mediators. IgE‐mediated mast cell activation can be modulated by different molecules, including several drugs. Herein, we investigated the immunomodulatory activity of the histone deacetylase inhibitor valproic acid (VPA) on IgE‐mediated mast cell activation. To this end, bone marrow‐derived mast cells (BMMC) were sensitized with IgE and treated with VPA followed by FcεRI cross‐linking. The results indicated that VPA reduced mast cell IgE‐dependent degranulation and cytokine release. VPA also induced a significant reduction in the cell surface expression of FcεRI and CD117, but not other mast cell surface molecules. Interestingly, VPA treatment inhibited the phosphorylation of PLCγ2, a key signaling molecule involved in IgE‐mediated degranulation and cytokine secretion. However, VPA did not affect the phosphorylation of other key components of the FcεRI signaling pathway, such as Syk, Akt, ERK1/2, or p38. Altogether, our data demonstrate that VPA affects PLCγ2 phosphorylation, which in turn decreases IgE‐mediated mast cell activation. These results suggest that VPA might be a key modulator of allergic reactions and might be a promising therapeutic candidate.

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Section: Resultsmentioning

confidence: 96%

The histone deacetylase inhibitor valproic acid attenuates phospholipase Cγ2 and IgE-mediated mast cell activation

Rodríguez-López

Soria-Castro

Campillo-Navarro

et al. 2020

Journal of Leukocyte Biology

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“…Contrary to established knowledge in extracellular bacteria, it appears that VPA promotes the control of infection by intracellular bacteria (Figure 3). Nieto-Patlán et al demonstrated that the employment of VPA induced a reduction in Mycobacterium tuberculosis load in IFN- γ -activated J774A.1 macrophages, which correlated with the rise in NO production due to an increase in the expression of iNOS (Figure 3) [64]. In line with this, VPA promotes the intracellular elimination through autophagy of M. bovis BCG or M. tuberculosis , in infected RAW264.7 macrophages and human alveolar macrophages, respectively (Figure 3) [65].…”

Section: Effects Of Valproic Acid On Cells Of the Innate Immune Rementioning

confidence: 99%

Exploring the Drug Repurposing Versatility of Valproic Acid as a Multifunctional Regulator of Innate and Adaptive Immune Cells

Soria-Castro

Schcolnik‐Cabrera

Rodríguez-López

et al. 2019

Journal of Immunology Research

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Valproic acid (VPA) is widely recognized for its use in the control of epilepsy and other neurological disorders in the past 50 years. Recent evidence has shown the potential of VPA in the control of certain cancers, owed in part to its role in modulating epigenetic changes through the inhibition of histone deacetylases, affecting the expression of genes involved in the cell cycle, differentiation, and apoptosis. The direct impact of VPA in cells of the immune system has only been explored recently. In this review, we discuss the effects of VPA in the suppression of some activation mechanisms in several immune cells that lead to an anti-inflammatory response. As expected, immune cells are not exempt from the effect of VPA, as it also affects the expression of genes of the cell cycle and apoptosis through epigenetic modifications. In addition to inhibiting histone deacetylases, VPA promotes RNA interference, activates histone methyltransferases, or represses the activation of transcription factors. However, during the infectious process, the effectiveness of VPA is subject to the biological nature of the pathogen and the associated immune response; this is because VPA can promote the control or the progression of the infection. Due to its various effects, VPA is a promising alternative for the control of autoimmune diseases and hypersensitivity and needs to be further explored.

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“…A similar pattern was also observed in groupers in the bH group. Notably in this regard, we also detected signi cant increases and decreases in the levels of IFNγ and TNF-α in the bL group, respectively, the former of which can enhance NO secretion by stimulating macrophages and inducing the production of nitric oxide synthase 31 . However, given that TNF-α showed an increase and decrease in the bL and bH groups, respectively, we were unable to determine whether TNF-α is involved in the regulation of NO production.…”

Section: Discussionmentioning

confidence: 57%

β-Conglycinin Regulates Intestinal Immunity through the CIITA-mediated MHC II-PI3K/Akt/mTOR Pathway in Hybrid Grouper: The Ameliorative Effects of Sodium Butyrate (NaB)

Yin

Liu

Tan

et al. 2021

Preprint

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We investigated the effects of low and high doses of 7S and the ameliorative effects of NaB (based on high-dose 7S) on the growth performance, serum immunity, distal histopathology, and CIITA-mediated MHC II-PI3K/Akt/mTOR pathway in hybrid groupers. The results revealed that the specific growth rate of groupers significantly increased, decreased, and increased in the low-level 7S (bL), high-level 7S (bH) high-level 7S plus NaB (bH-NaB) groups, respectively. The feed coefficient ratio was significantly increased in the bH and bH-NaB groups, whereas serum levels of IFN-γ, IL-1β, and TNF-α were upregulated in the bH group. The intestinal diameter/plica height ratio was significantly increased in the bH group. Furthermore, there were increases in nitric oxide, nitric oxide synthase (NOS), and peroxynitrite anion (ONOO−) in the bH group, and decreases in NOS and ONOO− in the bH-NaB group. The mRNA levels in distal intestine of TSC1, mTOR C2, CIITA, and CREB1 were significantly upregulated in all three treatment groups, whereas those of IKKα, Rheb, mTOR C1, mLST8, EIF4B, NFY, GILT, and AEP were upregulated and downregulated in the bH and bH-NaB groups, respectively. These indicate 7S has a regulatory effect on serum immunity and affect distal intestinal development by modulating hindgut injury-related parameters. Within the distal intestinal tract, 7S can induce intestinal inflammation by activating the CIITA-mediated MHC II-PI3K/Akt/mTOR pathway, which eventually manifests as a reduction in growth performance. Supplementing feed with NaB represents an effective approach for enhancing serum immunity, and also protects the intestines from damage caused by high-dose 7S.

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Valproic acid promotes a decrease in mycobacterial survival by enhancing nitric oxide production in macrophages stimulated with IFN-γ

Cited by 19 publications

References 16 publications

The histone deacetylase inhibitor valproic acid attenuates phospholipase Cγ2 and IgE-mediated mast cell activation

The histone deacetylase inhibitor valproic acid attenuates phospholipase Cγ2 and IgE-mediated mast cell activation

Exploring the Drug Repurposing Versatility of Valproic Acid as a Multifunctional Regulator of Innate and Adaptive Immune Cells

β-Conglycinin Regulates Intestinal Immunity through the CIITA-mediated MHC II-PI3K/Akt/mTOR Pathway in Hybrid Grouper: The Ameliorative Effects of Sodium Butyrate (NaB)

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