Leishmanial lipid suppresses the bacterial endotoxin-induced inflammatory response with attenuation of tissue injury in sepsis

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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Pretreatment with stress cortisol enhances the human systemic inflammatory response to bacterial endotoxin

Critical Care Medicine ◽

10.1097/00003246-200910000-00008 ◽

2009 ◽

Vol 37 (10) ◽

pp. 2727-2732 ◽

Cited By ~ 3

Author(s):

Mark P. Yeager ◽

Athos J. Rassias ◽

Patricia A. Pioli ◽

Michael L. Beach ◽

Kathleen Wardwell ◽

...

Keyword(s):

Inflammatory Response ◽

Systemic Inflammatory Response ◽

Bacterial Endotoxin

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Angiotensin II AT1 Receptor Blockade Decreases Lipopolysaccharide-Induced Inflammation in the Rat Adrenal Gland

Endocrinology ◽

10.1210/en.2008-0242 ◽

2008 ◽

Vol 149 (10) ◽

pp. 5177-5188 ◽

Cited By ~ 34

Author(s):

Enrique Sanchez-Lemus ◽

Yuki Murakami ◽

Ignacio M. Larrayoz-Roldan ◽

Armen J. Moughamian ◽

Jaroslav Pavel ◽

...

Keyword(s):

Gene Expression ◽

Angiotensin Ii ◽

Adrenal Gland ◽

Inflammatory Response ◽

Innate Immune ◽

Bacterial Endotoxin ◽

Receptor Blockade ◽

Tnf Α ◽

Antiinflammatory Effects ◽

Corticosterone Release

Peripheral administration of bacterial endotoxin [lipopolysaccharide (LPS)] to rodents produces an innate immune response and hypothalamic-pituitary-adrenal axis stimulation. Renin-angiotensin-aldosterone system inhibition by angiotensin II AT1 receptor blockade has antiinflammatory effects in the vasculature. We studied whether angiotensin II receptor blockers (ARBs) prevent the LPS response. We focused on the adrenal gland, one organ responsive to LPS and expressing a local renin-angiotensin-aldosterone system. LPS (50 μg/kg, ip) produced a generalized inflammatory response with increased release of TNF-α and IL-6 to the circulation, enhanced adrenal aldosterone synthesis and release, and enhanced adrenal cyclooxygenase-2, IL-6, and TNF-α gene expression. ACTH and corticosterone release were also increased by LPS. Pretreatment with the ARB candesartan (1 mg/kg·d, sc for 3 d before the LPS administration) decreased LPS-induced cytokine release to the circulation, adrenal aldosterone synthesis and release, and cyclooxygenase-2 and IL-6 gene expression. Candesartan did not prevent the LPS-induced ACTH and corticosterone release. Our results suggest that AT1 receptors are essential for the development of the full innate immune and stress responses to bacterial endotoxin. The ARB decreased the general peripheral inflammatory response to LPS, partially decreased the inflammatory response in the adrenal gland, prevented the release of the pro-inflammatory hormone aldosterone, and protected the antiinflammatory effects of glucocorticoid release. An unrestricted innate immune response to the bacterial endotoxin may have deleterious effects for the organism and may lead to development of chronic inflammatory disease. We postulate that the ARBs may have therapeutic effects on inflammatory conditions.

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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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Hyaluronan fragments produced during tissue injury: A signal amplifying the inflammatory response

Archives of Biochemistry and Biophysics ◽

10.1016/j.abb.2019.01.015 ◽

2019 ◽

Vol 663 ◽

pp. 228-238 ◽

Cited By ~ 5

Author(s):

Angela Avenoso ◽

Giuseppe Bruschetta ◽

Angela D'Ascola ◽

Michele Scuruchi ◽

Giuseppe Mandraffino ◽

...

Keyword(s):

Inflammatory Response ◽

Tissue Injury

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Proinflammatory Responses of Heme in Alveolar Macrophages: Repercussion in Lung Hemorrhagic Episodes

Mediators of Inflammation ◽

10.1155/2013/946878 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 9

Author(s):

Rafael L. Simões ◽

Maria Augusta Arruda ◽

Cláudio Canetti ◽

Carlos H. Serezani ◽

Iolanda M. Fierro ◽

...

Keyword(s):

Inflammatory Response ◽

Alveolar Macrophages ◽

Nuclear Translocation ◽

Tissue Injury ◽

Proinflammatory Responses ◽

Proinflammatory Molecule ◽

Free Heme ◽

Inflammatory Processes ◽

Lung Hemorrhage ◽

And Function

Clinical and experimental observations have supported the notion that free heme released during hemorrhagic and hemolytic episodes may have a major role in lung inflammation. With alveolar macrophages (AM) being the main line of defense in lung environments, the influence of free heme on AM activity and function was investigated. We observed that heme in a concentration range found during hemolytic episodes (3–30 μM) elicits AM to present a proinflammatory profile, stimulating reactive oxygen species (ROS) and nitric oxide (NO) generation and inducing IL-1β, IL-6, and IL-10 secretion. ROS production is NADPH oxidase-dependent, being inhibited by DPI and apocynin, and involves p47 subunit phosphorylation. Furthermore, heme induces NF-κB nuclear translocation, iNOS, and also HO-1 expression. Moreover, AM stimulated with free heme show enhanced phagocytic and bactericidal activities. Taken together, the data support a dual role for heme in the inflammatory response associated with lung hemorrhage, acting as a proinflammatory molecule that can either act as both an adjuvant of the innate immunity and as an amplifier of the inflammatory response, leading tissue injury. The understanding of heme effects on pulmonary inflammatory processes can lead to the development of new strategies to ameliorate tissue damage associated with hemorrhagic episodes.

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Angiotensin-Converting Enzyme 2 as a Possible Correlation between COVID-19 and Periodontal Disease

Applied Sciences ◽

10.3390/app10186224 ◽

2020 ◽

Vol 10 (18) ◽

pp. 6224 ◽

Cited By ~ 1

Author(s):

Leonardo Mancini ◽

Vincenzo Quinzi ◽

Stefano Mummolo ◽

Giuseppe Marzo ◽

Enrico Marchetti

Keyword(s):

Angiotensin Ii ◽

Inflammatory Response ◽

Angiotensin Converting Enzyme ◽

Transforming Growth Factor ◽

Tissue Injury ◽

Interleukin 2 ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Cell Functions

SARS-CoV-2 propagation in the world has led to rapid growth and an acceleration in the discoveries and publications of various interests. The main focus of a consistent number of studies has been the role of angiotensin-converting enzyme 2 (ACE2) in binding the virus and its role in expression of the inflammatory response after transmission. ACE2 is an enzyme involved in the renin–angiotensin system (RAS), whose key role is to regulate and counter angiotensin-converting enzyme (ACE), reducing the amount of angiotensin II and increasing angiotensin 1–7 (Ang1–7), making it a promising drug target for treating cardiovascular diseases. The classical RAS axis, formed by ACE, angiotensin II (Ang II), and angiotensin receptor type 1 (AT1), activates several cell functions and molecular signalling pathways related to tissue injury and inflammation. In contrast, the RAS axis composed of ACE2, Ang1–7, and Mas receptor (MasR) exerts the opposite effect concerning the inflammatory response and tissue fibrosis. Recent studies have shown the presence of the RAS system in periodontal sites where osteoblasts, fibroblasts, and osteoclasts are involved in bone remodelling, suggesting that the role of ACE2 might have a fundamental function in the under- or overexpression of cytokines such as interleukin-6 (IL-6), interleukin-7 (IL-7), tumour necrosis factor alpha (TNF-α), interleukin-2 (IL-2), interleukin-1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta (TGF-β), associated with a periodontal disorder, mainly during coinfection with SARS-CoV-2, where ACE2 is underexpressed and cannot form the ACE2–Ang1–7–MasR axis. This renders the patient unresponsive to an inflammatory process, facilitating periodontal loss.

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