Epigenetic immune-modulation by Histone Deacetylase Activity (HDAC) of tissue and organ regeneration in Xenopus laevis

AbstractIn the present work we propose to shed light on the epigenetic control of immune mechanisms involved during Xenopus tail regeneration. Here we show that the first 24 hour post amputation (hpa), which exclusively encompasses the first wave of myeloid differentiation, are crucial to epigenetically modulate the regenerative ability of Xenopus tadpoles. During this developmental window, HDAC activity was shown to be necessary for the proper establishment of myeloid cells dynamics in the regenerative bud, mainly contributing to modulate the behavior of monocytes/macrophages and neutrophils as well the mRNA expression pattern of the main myeloid markers, such as LURP, MPOX, Spib and mmp7. In addition, we functionally bridge the spatial and temporal dynamics of lipid droplets, the main platform of lipid mediators synthesis in myeloid cells during the inflammatory response, and the regenerative ability of Xenopus tadpoles showing that 15-LOX activity is a key player during tail regeneration. Taken together our results support a role for the epigenetic control of inflammatory response during tissue and organ regeneration, which may positively impact translational approaches for regenerative medicine.Summary statementWe propose that Epigenetic mechanisms HDAC-dependent can control myeloid cells behavior upon tissue injury and that HDAC inhibitors may be used for tissue regeneration in translational studies.

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Monocytes and macrophages in tissue repair: Implications for immunoregenerative biomaterial design

Experimental Biology and Medicine ◽

10.1177/1535370216650293 ◽

2016 ◽

Vol 241 (10) ◽

pp. 1084-1097 ◽

Cited By ~ 154

Author(s):

Molly E Ogle ◽

Claire E Segar ◽

Sraeyes Sridhar ◽

Edward A Botchwey

Keyword(s):

Inflammatory Response ◽

Immune Cells ◽

Tissue Repair ◽

Tissue Injury ◽

Critical Role ◽

Myeloid Cells ◽

Innate Immune ◽

Innate Immune Cells ◽

Signaling Systems ◽

Monocytes And Macrophages

Monocytes and macrophages play a critical role in tissue development, homeostasis, and injury repair. These innate immune cells participate in guiding vascular remodeling, stimulation of local stem and progenitor cells, and structural repair of tissues such as muscle and bone. Therefore, there is a great interest in harnessing this powerful endogenous cell source for therapeutic regeneration through immunoregenerative biomaterial engineering. These materials seek to harness specific subpopulations of monocytes/macrophages to promote repair by influencing their recruitment, positioning, differentiation, and function within a damaged tissue. Monocyte and macrophage phenotypes span a continuum of inflammatory (M1) to anti-inflammatory or pro-regenerative cells (M2), and their heterogeneous functions are highly dependent on microenvironmental cues within the injury niche. Increasing evidence suggests that division of labor among subpopulations of monocytes and macrophages could allow for harnessing regenerative functions over inflammatory functions of myeloid cells; however, the complex balance between necessary functions of inflammatory versus regenerative myeloid cells remains to be fully elucidated. Historically, biomaterial-based therapies for promoting tissue regeneration were designed to minimize the host inflammatory response; although, recent appreciation for the roles that innate immune cells play in tissue repair and material integration has shifted this paradigm. A number of opportunities exist to exploit known signaling systems of specific populations of monocytes/macrophages to promote repair and to better understand the biological and pathological roles of myeloid cells. This review seeks to outline the characteristics of distinct populations of monocytes and macrophages, identify the role of these cells within diverse tissue injury niches, and offer design criteria for immunoregenerative biomaterials given the intrinsic inflammatory response to their implantation.

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Epigenetic control of myeloid cells behavior by Histone Deacetylase activity (HDAC) during tissue and organ regeneration in Xenopus laevis

Developmental & Comparative Immunology ◽

10.1016/j.dci.2020.103840 ◽

2021 ◽

Vol 114 ◽

pp. 103840

Author(s):

Nathalia Pentagna ◽

Thayse Pinheiro da Costa ◽

Fellipe Soares dos Santos Cardoso ◽

Fernanda Martins de Almeida ◽

Ana Maria Blanco Martinez ◽

...

Keyword(s):

Xenopus Laevis ◽

Histone Deacetylase ◽

Myeloid Cells ◽

Epigenetic Control ◽

Organ Regeneration

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HDAC inhibitors: Targets for tumor therapy, immune modulation and lung diseases

Translational Oncology ◽

10.1016/j.tranon.2021.101312 ◽

2022 ◽

Vol 16 ◽

pp. 101312

Author(s):

Geetha Shanmugam ◽

Sudeshna Rakshit ◽

Koustav Sarkar

Keyword(s):

Lung Diseases ◽

Immune Modulation ◽

Tumor Therapy ◽

Hdac Inhibitors

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Trimethylamine N-oxide promotes hyperlipidemia acute pancreatitis via inflammatory response

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2021-0421 ◽

2021 ◽

pp. 1-7

Author(s):

Guodong Yang ◽

Xiaoying Zhang

Keyword(s):

Acute Pancreatitis ◽

Inflammatory Response ◽

Tissue Injury ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Pancreatic Injury ◽

Pancreatic Tissue ◽

Lipoprotein Cholesterol ◽

Model Group ◽

New Ideas

Trimethylamine N-oxide (TMAO), a metabolite of gut microbiota, is involved in the regulation of lipid metabolism and inflammatory response; however, the role of TMAO in hyperlipidemia acute pancreatitis (HAP) is not clear. In this study, HAP mice were used as an animal model to explore the effects and possible mechanism of TMAO on HAP, which may provide new ideas for the treatment of HAP. Results found that the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, nonestesterified fatty acid, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, α-amylase, TMAO, and flavin-containing monooxygenase 3 were significantly increased, the levels of high-density lipoprotein cholesterol and insulin were significantly decreased, and there was an obvious pancreatic injury and inflammatory response in the model group. The choline analogue 3,3-dimethyl-1-butanol (DMB) treatment reversed the changes of serum biochemical parameters, alleviated the pancreatic tissue injury, and reduced the levels of inflammatory cytokines. Further studies of toll-like receptor (TLR)/p-glycoprotein 65 (p65) pathway found that the expressions of TLR2, TLR4, and p-p65/p65 in the model group were significantly increased, which was more obvious after Escherichia coli (Migula) Castellani & Chalmers treatment, while activation of the TLR/p65 pathway was inhibited by DMB. The results indicated that TMAO promotes HAP by promoting inflammatory response through TLR/p65 signaling pathway, suggesting that TMAO may be a potential target of HAP.

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Sepsis Syndrome

The Brigham Intensive Review of Internal Medicine ◽

10.1093/med/9780199358274.003.0039 ◽

2014 ◽

pp. 395-402

Author(s):

Joshua A. Englert ◽

Rebecca Marlene Baron

Keyword(s):

Immune System ◽

Inflammatory Response ◽

Innate Immune System ◽

Tissue Injury ◽

Treatment Strategies ◽

Sepsis Syndrome ◽

Clinical Syndrome ◽

High Morbidity ◽

Early Management ◽

Inflammatory State

Sepsis is a clinical syndrome characterized by systemic inflammation leading to tissue injury that arises as a complication of an infection. According to current paradigms, sepsis arises as a result of the infection of a normally sterile body compartment. Infection leads to activation of the innate immune system to produce a systemic inflammatory response. This response is a necessary component of the body's defense against infection under normal conditions, but it is the lack of regulation of this response that is central to the pathogenesis of sepsis. As discussed in more detail below, this dysregulated inflammatory state can lead to tissue injury and dysfunction in organs not involved in the original infectious insult. Although sepsis remains a condition with exceedingly high morbidity and mortality, recent early management and treatment strategies have demonstrated exciting improvements in overall outcomes.

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Sepsis Syndrome

Mayo Clinic Infectious Diseases Board Review ◽

10.1093/med/9780199827626.003.0027 ◽

2012 ◽

pp. 274-279

Author(s):

Andrew D Badley

Keyword(s):

Systemic Inflammatory Response Syndrome ◽

Inflammatory Response ◽

Physical Examination ◽

Supportive Care ◽

Tissue Injury ◽

Tissue Perfusion ◽

Sepsis Syndrome ◽

Systemic Response ◽

Immune Mediated ◽

Patient’S History

Systemic inflammatory response syndrome (SIRS) is the specific host systemic response that may be elicited by various stimuli, including infection, burns, pancreatitis, ischemia, trauma, hemorrhage, immune-mediated tissue injury, and exogenous stimuli. 2. Sepsis is SIRS resulting from infection. Sepsis syndrome is sepsis with altered tissue perfusion of vital organs (resulting in oliguria, hypoxemia, elevated levels of lactate, or altered mentation or any combination of these conditions) When a patient has SIRS, the objective is to define its cause. If SIRS is caused by infection, appropriate antibiotics must be administered and supportive care guided by the patient's history and physical examination.

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Role of ATP-sensitive potassium channels and inflammatory response of basilar artery smooth muscle cells in subarachnoid hemorrhage of rabbit and immune-modulation by shikonin

Food and Chemical Toxicology ◽

10.1016/j.fct.2019.110804 ◽

2019 ◽

Vol 134 ◽

pp. 110804 ◽

Cited By ~ 1

Author(s):

Xianqing Shi ◽

Lirong Zhen ◽

Hao Ding ◽

Jing Chen ◽

Songsong Zhang ◽

...

Keyword(s):

Smooth Muscle ◽

Subarachnoid Hemorrhage ◽

Potassium Channels ◽

Inflammatory Response ◽

Smooth Muscle Cells ◽

Basilar Artery ◽

Immune Modulation ◽

Muscle Cells

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PKCα-LSD1-NF-κB-Signaling Cascade Is Crucial for Epigenetic Control of the Inflammatory Response

Molecular Cell ◽

10.1016/j.molcel.2018.01.002 ◽

2018 ◽

Vol 69 (3) ◽

pp. 398-411.e6 ◽

Cited By ~ 22

Author(s):

Dongha Kim ◽

Hye Jin Nam ◽

Wonhwa Lee ◽

Hwa Young Yim ◽

Jun-Yeong Ahn ◽

...

Keyword(s):

Inflammatory Response ◽

Signaling Cascade ◽

Epigenetic Control

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Repair and recovery mechanisms following critical illness

10.1093/med/9780199600830.003.0309 ◽

2016 ◽

Author(s):

Geoffrey Bellingan ◽

Brijesh V. Patel

Keyword(s):

Critical Illness ◽

Inflammatory Response ◽

Inflammatory Responses ◽

Tissue Injury ◽

Structure And Function ◽

Tissue Structure ◽

Inflammatory Activation ◽

Recovery Mechanisms ◽

And Function

Inflammation is the beneficial host response to foreign challenge or tissue injury that ultimately leads to the restoration of tissue structure and function. Critical illness is associated with an overwhelming and prolonged inflammatory activation. Resolution of the inflammatory response is an active process that requires removal of the inciting stimuli, cessation of the pro-inflammatory response, a timely coordinated removal of tissue leukocyte infiltration, a conversion from ‘toxic’ to reparative tissue environment, and restoration of normal tissue structure and function. Mortality may result from deficits in these resolution mechanisms. Improved delivery of critical care through prevention of harm and removal of stimuli has already delivered significant mortality benefits. Most critically-ill patients present with uncontrolled inflammation, hence anti-inflammatory strategies ameliorating this response are likely to be too late and thus futile. Rather, strategies augmenting endogenous pathways involved in the control and appropriate curtailment of such inflammatory responses may promote resolution, repair, and catabasis. Recent evidence showing that inflammation does not simply ‘fizzle out’, but its resolution involves an active and coordinated series of events. Dysfunction of these resolution checkpoints alters the normal inflammatory pathway, and is implicated in the induction and maintenance of states such as ARDS and sepsis. Improved understanding of resolution biology should provide translational pathways to not only improve survival, but also to prevent long-term morbidity resulting from tissue damage.

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