Butyrate and propionate induced activated or non-activated neutrophil apoptosis via HDAC inhibitor activity but without activating GPR-41/GPR-43 pathways

Aoyama, Masayuki; Kotani, Joji; Usami, Makoto

doi:10.1016/j.nut.2009.07.006

Cited by 200 publications

(142 citation statements)

References 39 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…Recently, HDAC inhibition was partially GPR43 dependent in colon tissue, 28 but other researchers have observed HDAC inhibition in a GPR43-independent manner. 29 Although we observed high expression of GPR43 in our model, its expression has been reported as minimal or null in kidney tissue. 30,31 Thus, we believe that acetate might be regulating the inflammatory process by regulating epigenetic modification in a GPR-independent manner.…”

Section: Discussioncontrasting

confidence: 60%

Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion

Andrade-Oliveira

Amano

Corrêa-Costa

et al. 2015

Journal of the American Society of Nephrology

416

330

View full text Add to dashboard Cite

Short-chain fatty acids (SCFAs) are fermentation end products produced by the intestinal microbiota and have anti-inflammatory and histone deacetylase-inhibiting properties. Recently, a dual relationship between the intestine and kidneys has been unraveled. Therefore, we evaluated the role of SCFA in an AKI model in which the inflammatory process has a detrimental role. We observed that therapy with the three main SCFAs (acetate, propionate, and butyrate) improved renal dysfunction caused by injury. This protection was associated with low levels of local and systemic inflammation, oxidative cellular stress, cell infiltration/activation, and apoptosis. However, it was also associated with an increase in autophagy. Moreover, SCFAs inhibited histone deacetylase activity and modulated the expression levels of enzymes involved in chromatin modification. In vitro analyses showed that SCFAs modulated the inflammatory process, decreasing the maturation of dendritic cells and inhibiting the capacity of these cells to induce CD4 + and CD8 + T cell proliferation. Furthermore, SCFAs ameliorated the effects of hypoxia in kidney epithelial cells by improving mitochondrial biogenesis. Notably, mice treated with acetate-producing bacteria also had better outcomes after AKI. Thus, we demonstrate that SCFAs improve organ function and viability after an injury through modulation of the inflammatory process, most likely via epigenetic modification.

show abstract

Section: Discussioncontrasting

confidence: 60%

Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion

Andrade-Oliveira

Amano

Corrêa-Costa

et al. 2015

Journal of the American Society of Nephrology

416

330

View full text Add to dashboard Cite

show abstract

“…In contrast, in neutrophils obtained from healthy human volunteers, butyrate increased apoptosis irrespective of their activation state, by factors other than MAPK and GPR, and their mechanisms probably relate to their histone deacetylase inhibition activity, which may control a1 mRNA expression (128) .…”

Section: Apoptosismentioning

confidence: 76%

From the gut to the peripheral tissues: the multiple effects of butyrate

et al. 2010

View full text Add to dashboard Cite

Butyrate is a natural substance present in biological liquids and tissues. The present paper aims to give an update on the biological role of butyrate in mammals, when it is naturally produced by the gastrointestinal microbiota or orally ingested as a feed additive. Recent data concerning butyrate production delivery as well as absorption by the colonocytes are reported. Butyrate cannot be detected in the peripheral blood, which indicates fast metabolism in the gut wall and/or in the liver. In physiological conditions, the increase in performance in animals could be explained by the increased nutrient digestibility, the stimulation of the digestive enzyme secretions, a modification of intestinal luminal microbiota and an improvement of the epithelial integrity and defence systems. In the digestive tract, butyrate can act directly (upper gastrointestinal tract or hindgut) or indirectly (small intestine) on tissue development and repair. Direct trophic effects have been demonstrated mainly by cell proliferation studies, indicating a faster renewal of necrotic areas. Indirect actions of butyrate are believed to involve the hormono-neuro-immuno system. Butyrate has also been implicated in down-regulation of bacteria virulence, both by direct effects on virulence gene expression and by acting on cell proliferation of the host cells. In animal production, butyrate is a helpful feed additive, especially when ingested soon after birth, as it enhances performance and controls gut health disorders caused by bacterial pathogens. Such effects could be considered for new applications in human nutrition

show abstract

“…Of interest, here is the notion that HDACIs can induce apoptosis on neutrophils, 33 and this effect contributes to their profile as anti-inflammatory compounds. To assess if AnxA1 mediated these actions, we used bone marrow cells from WT and AnxA1 À / À mice, and incubated them with VPA, SB or TSA for 6 h. Apoptosis was studied specifically in the Ly6G þ population (Figure 3a).…”

Section: Resultsmentioning

confidence: 99%

“…The selective FPR2 antagonist WRW 4 was purchased from Calbiochem, Nottingham, UK. The PKC inhibitor (PKC [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] ) and the protein phosphatase 2 inhibitor (okadaic acid) were purchased from Tocris Bioscience, Bristol, UK.…”

Section: Methodsmentioning

confidence: 99%

Gene expression signature-based approach identifies a pro-resolving mechanism of action for histone deacetylase inhibitors

2012

View full text Add to dashboard Cite

Despite several therapies are currently available to treat inflammatory diseases, new drugs to treat chronic conditions with less side effects and lower production costs are still needed. An innovative approach to drug discovery, the Connectivity Map (CMap), shows how integrating genome-wide gene expression data of drugs and diseases can accelerate this process. Comparison of genome-wide gene expression data generated with Annexin A1 (AnxA1) with the CMap revealed significant alignment with gene profiles elicited by histone deacetylase inhibitors (HDACIs), what made us to hypothesize that AnxA1 might mediate the anti-inflammatory actions of HDACIs. Addition of HDACIs (valproic acid, sodium butyrate and thricostatin A) to mouse macrophages caused externalization of AnxA1 with concomitant inhibition of cytokine gene expression and release, events that occurred independently since this inhibition was retained in AnxA1 null macrophages. However, novel AnxA1-mediated functions for HDACIs could be unveiled, including promotion of neutrophil apoptosis and macrophage phagocytosis, both steps crucial for effective resolution of inflammation. In a model of acute resolving inflammation, administration of valproic acid and sodium butyrate to mice at the peak of disease accelerated resolution processes in wild type, but much more modestly in AnxA1 null mice. Deeper analyses revealed a role for endogenous AnxA1 in the induction of neutrophil death in vivo by HDACIs. In summary, interrogation of the CMap revealed an unexpected association between HDACIs and AnxA1 that translated in mechanistic findings with particular impact on the processes that regulate the resolution of inflammation. We propose non-genomic modulation of AnxA1 in immune cells as a novel mechanism of action for HDACIs, which may underlie their reported efficacy in models of chronic inflammatory pathologies.

show abstract

Butyrate and propionate induced activated or non-activated neutrophil apoptosis via HDAC inhibitor activity but without activating GPR-41/GPR-43 pathways

Cited by 200 publications

References 39 publications

Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion

Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion

From the gut to the peripheral tissues: the multiple effects of butyrate

Gene expression signature-based approach identifies a pro-resolving mechanism of action for histone deacetylase inhibitors

Contact Info

Product

Resources

About