scholarly journals Role of Lactate in Inflammatory Processes: Friend or Foe

2022 ◽  
Vol 12 ◽  
Author(s):  
Carolina Manosalva ◽  
John Quiroga ◽  
Alejandra I. Hidalgo ◽  
Pablo Alarcón ◽  
Nicolás Anseoleaga ◽  
...  
Keyword(s):  
Inflammatory Process ◽  
Inflammatory Mediator ◽  
Waste Product ◽  
Pathological Process ◽  
Extracellular Acidification ◽  
Post Translational Modifications ◽  
Transcription Factor Activation ◽  
Inflammatory Processes ◽  
G Protein Coupled

During an inflammatory process, shift in the cellular metabolism associated with an increase in extracellular acidification are well-known features. This pH drop in the inflamed tissue is largely attributed to the presence of lactate by an increase in glycolysis. In recent years, evidence has accumulated describing the role of lactate in inflammatory processes; however, there are differences as to whether lactate can currently be considered a pro- or anti-inflammatory mediator. Herein, we review these recent advances on the pleiotropic effects of lactate on the inflammatory process. Taken together, the evidence suggests that lactate could exert differential effects depending on the metabolic status, cell type in which the effects of lactate are studied, and the pathological process analyzed. Additionally, various targets, including post-translational modifications, G-protein coupled receptor and transcription factor activation such as NF-κB and HIF-1, allow lactate to modulate signaling pathways that control the expression of cytokines, chemokines, adhesion molecules, and several enzymes associated with immune response and metabolism. Altogether, this would explain its varied effects on inflammatory processes beyond its well-known role as a waste product of metabolism.

scholarly journals The Contribution of Formyl Peptide Receptor Dysfunction to the Course of Neuroinflammation: A Potential Role in the Brain Pathology

2020 ◽  
Vol 18 (3) ◽  
pp. 229-249 ◽  
Author(s):  
Ewa Trojan ◽  
Natalia Bryniarska ◽  
Monika Leśkiewicz ◽  
Magdalena Regulska ◽  
Katarzyna Chamera ◽  
...  
Keyword(s):  
Potential Role ◽  
Membrane Receptors ◽  
Formyl Peptide Receptor ◽  
Proinflammatory Response ◽  
Formyl Peptide ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
G Protein Coupled ◽  
The Brain

: Chronic inflammatory processes within the central nervous system (CNS) are in part responsible for the development of neurodegenerative and psychiatric diseases. These processes are associated with, among other things, the increased and disturbed activation of microglia and the elevated production of proinflammatory factors. Recent studies indicated that the disruption of the process of resolution of inflammation (RoI) may be the cause of CNS disorders. It is shown that the RoI is regulated by endogenous molecules called specialized pro-resolving mediators (SPMs), which interact with specific membrane receptors. Some SPMs activate formyl peptide receptors (FPRs), which belong to the family of seven-transmembrane G protein-coupled receptors. These receptors take part not only in the proinflammatory response but also in the resolution of the inflammation process. Therefore, the activation of FPRs might have complex consequences. : This review discusses the potential role of FPRs, and in particular the role of FPR2 subtype, in the brain under physiological and pathological conditions and their involvement in processes underlying neurodegenerative and psychiatric disorders as well as ischemia, the pathogenesis of which involves the dysfunction of inflammatory processes.

scholarly journals Shedding light on the role of CX3CR1 in the pathogenesis of schizophrenia

2021 ◽  
Author(s):  
Katarzyna Chamera ◽  
Magdalena Szuster-Głuszczak ◽  
Agnieszka Basta-Kaim
Keyword(s):  
Experimental Studies ◽  
Physiological Processes ◽  
Unique System ◽  
The Family ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
G Protein Coupled ◽  
The Brain ◽  
Brain Homeostasis

AbstractSchizophrenia has a complex and heterogeneous molecular and clinical picture. Over the years of research on this disease, many factors have been suggested to contribute to its pathogenesis. Recently, the inflammatory processes have gained particular interest in the context of schizophrenia due to the increasing evidence from epidemiological, clinical and experimental studies. Within the immunological component, special attention has been brought to chemokines and their receptors. Among them, CX3C chemokine receptor 1 (CX3CR1), which belongs to the family of seven-transmembrane G protein-coupled receptors, and its cognate ligand (CX3CL1) constitute a unique system in the central nervous system. In the view of regulation of the brain homeostasis through immune response, as well as control of microglia reactivity, the CX3CL1–CX3CR1 system may represent an attractive target for further research and schizophrenia treatment. In the review, we described the general characteristics of the CX3CL1–CX3CR1 axis and the involvement of this signaling pathway in the physiological processes whose disruptions are reported to participate in mechanisms underlying schizophrenia. Furthermore, based on the available clinical and experimental data, we presented a guide to understanding the implication of the CX3CL1–CX3CR1 dysfunctions in the course of schizophrenia.

scholarly journals State of collagenolysis in experimental periodontitis of bacterial-immune genesis and its correction with flavonol

2021 ◽  
Vol 26 (2) ◽  
pp. 26-32
Author(s):  
A.Ye. Demkovych ◽  
Yu.I. Bondarenko ◽  
O.O. Fastovets ◽  
A.O. Hrad ◽  
P.A. Hasiuk ◽  
...  
Keyword(s):  
Inflammatory Process ◽  
Soft Tissues ◽  
Pathological Process ◽  
Calibration Graph ◽  
The State ◽  
Experimental Animals ◽  
Periodontal Tissues ◽  
Tissue Homogenates ◽  
Experimental Periodontitis

The article presents an assessment of the dynamics of changes in the content of the marker of collagenolysis – free oxyproline in the homogeniate of soft tissues and bone in experimental bacterial-immune periodontitis and elucidation of the effect of flavonol quercetin on these indicators. The aim of this study was to determine the role of cytokinogenesis and the effect of flavonol on it in the pathogenesis, development and course of experimental periodontitis. During the experiment, a fragment of the mandible was taken from the animals, from which the soft tissues and bone were carefully separated. The state of collagen was determined by the content of free oxyproline in the soft and bone tissues. The concentration was determined according to the calibration graph and expressed in μmol/g. The results of studies of the indicators of the state of biopolymers of connective tissue structures of periodontium on the 7th, 14th and 30th day of experimental bacterial-immune periodontitis and after its correction with flavonol (from the 7th to the 14th day of the experiment) are presented. The data on the nature of changes in the content of collagen monomers in the process of formation of the inflammatory focus in the periodontal complex are given. During the acute phase of the inflammatory process in rats there was revealed a slight increase in blood free oxyproline in bone homogenate and homogenate of soft periodontal tissues, on the 14th day the dynamics continued to increase, at a later stage of the experiment, namely on the 30th day, increase in bone resorption continued  as compared to the 7th and 14th day. During the correction of disorders resulted from  the development of this pathological process there was a decrease in the level of free oxyproline in the bone homogenate and homogenate of soft tissues of mandibular periodontium, as compared to the same indicators of animals who did not receive quercetin on the 14th day. The use of flavonol quercetin, which, by affecting immune processes, limited the inflammatory response in periodontal tissues and stabilized collagenolysis processes in periodontal tissues was manifested by a decrease in free oxyproline in bone and soft tissue homogenates of experimental animals.

Rho GTPase Rac1 is critical for neutrophil migration into the lung

Blood ◽  
2006 ◽  
Vol 109 (3) ◽  
pp. 1257-1264 ◽  
Author(s):  
Marie-Dominique Filippi ◽  
Kathleen Szczur ◽  
Chad E. Harris ◽  
Pierre-Yves Berclaz
Keyword(s):  
Inflammatory Process ◽  
Rho Gtpase ◽  
Bone Marrow Cells ◽  
Neutrophil Migration ◽  
Neutrophil Recruitment ◽  
In Vivo Models ◽  
Rac1 Activity ◽  
Inflammatory Processes

Abstract Neutrophils are critical in the inflammatory process by moving rapidly to tissue sites of inflammation. Members of the small Rho GTPase family, Rac1, Rac2, CDC42, and RhoA, are central regulators of cell migration by cytoskeleton rearrangement. The role of Rac1 in neutrophil migration related to inflammatory processes has remained elusive and has yet to be determined in physiologic in vivo models. We previously demonstrated a role for Rac1 in tail retraction. Here, we present evidence that Rac1-mediated uropod formation may be due to crosstalk with a related Rho GTPase RhoA. To assess the physiologic relevance of these findings, we used adoptive transfer of Rac1flox/flox bone marrow cells which allows postengraftment in vivo deletion of Rac1 only in blood cells. We examined the specific role of Rac1 in neutrophil migration into the lung during the inflammatory process induced by formyl-methionyl-leucyl-phenylalanine exposure. The loss of Rac1 activity in neutrophils is associated with a significant decreased neutrophil recruitment into lung alveolar and attenuation of emphysematous lesions. Overall, this study suggests that Rac1 is a physiologic integrator of signals for neutrophil recruitment into lung tissue during an inflammatory response.

scholarly journals Role of BET Proteins in Inflammation and CNS Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Lei Liu ◽  
Changjun Yang ◽  
Eduardo Candelario-Jalil
Keyword(s):  
Inflammatory Process ◽  
Structural Features ◽  
Pathological Process ◽  
Cns Disorders ◽  
Cns Diseases ◽  
Master Regulators ◽  
Novel Therapeutic

Bromodomain and extra-terminal domain (BET) proteins consist of four mammalian members (BRD2, BRD3, BRD4, and BRDT), which play a pivotal role in the transcriptional regulation of the inflammatory response. Dysregulated inflammation is a key pathological process in various CNS disorders through multiple mechanisms, including NF-κB and Nrf2 pathways, two well-known master regulators of inflammation. A better mechanistic understanding of the BET proteins’ role in regulating the inflammatory process is of great significance since it could reveal novel therapeutic targets to reduce neuroinflammation associated with many CNS diseases. In this minireview, we first outline the structural features of BET proteins and summarize genetic and pharmacological approaches for BET inhibition, including novel strategies using proteolysis-targeting chimeras (PROTACs). We emphasize in vitro and in vivo evidence of the interplay between BET proteins and NF-κB and Nrf2 signaling pathways. Finally, we summarize recent studies showing that BET proteins are essential regulators of inflammation and neuropathology in various CNS diseases.

scholarly journals Interpretation of C-Reactive Protein Concentrations in Critically Ill Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Christophe Lelubre ◽  
Sophie Anselin ◽  
Karim Zouaoui Boudjeltia ◽  
Patrick Biston ◽  
Michaël Piagnerelli
Keyword(s):  
Clinical Practice ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Inflammatory Process ◽  
Early Recognition ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Pathophysiological Role ◽  
Inflammatory Processes

Infection is often difficult to recognize in critically ill patients because of the marked coexisting inflammatory process. Lack of early recognition prevents timely resuscitation and effective antimicrobial therapy, resulting in increased morbidity and mortality. Measurement of a biomarker, such as C-reactive protein (CRP) concentration, in addition to history and physical signs, could facilitate diagnosis. Although frequently measured in clinical practice, few studies have reported on the pathophysiological role of this biomarker and its predictive value in critically ill patients. In this review, we discuss the pathophysiological role of CRP and its potential interpretation in the inflammatory processes observed in critically ill patients.

IMMUNOLOGICAL CHARACTERISTICS OF THE INFLAMMATORY PROCESS IN THE PULP

2021 ◽  
Vol 2 (1) ◽  
pp. 11-14
Author(s):  
Gilyazeva V.V.
Keyword(s):  
Connective Tissue ◽  
Basement Membrane ◽  
Inflammatory Process ◽  
Pathological Process ◽  
Tooth Pulp ◽  
Pulp Inflammation ◽  
Inflammatory Processes ◽  
Cd 68 ◽  
Main Component

The paper presents the immunological characteristics of the pathological process of the tooth pulp of an inflammatory nature. The content of key markers of inflammatory processes was studied: CD-68, which plays a role in the phagocytic activity of tissue macrophages and type 4 collagen - the main component of the basement membrane of epithelial cells, found in the wall of arterial vessels and the intrinsic substance of connective tissue. An increase in the number of macrophages and a significant increase in the expression of type 4 collagen in pulp inflammation were found. It has been shown that the inflammatory reaction in the pulp is characterized by a sufficient immunological potential for the involvement of a complex of periapical and periradicular tissues in the pathological process and its subsequent long-term completion.

scholarly journals ROLE OF SUBSTANCE P IN PANCREATITIS AND ASSOCIATED DISEASES

2021 ◽  
Vol 9 (5) ◽  
pp. 580-590
Author(s):  
Vaishnavi Sundar ◽  
◽  
Shalini Ramasamy ◽  
Sanjana Vimal ◽  
Anupam Dutta ◽  
...  
Keyword(s):  
Substance P ◽  
Neurogenic Inflammation ◽  
Vital Role ◽  
C Fibers ◽  
Inflammatory Processes ◽  
Plasma Leakage ◽  
Neurokinin 1 ◽  
G Protein Coupled ◽  
Crucial Part

Substance P (SP) is a neuropeptide that has its place in the tachykinin family and helps in the transmission of neurogenic signals. SP is also a neuromodulator that plays a crucial part in pain during inflammatory processes. It is produced by the capsaicin-sensitive unmyelinated C fibers sensory neurons by the central and peripheral nervous systems. Substance P is known as a critical primary responder to most of the extreme stimuli, i.e., specifically those with the ability to destabilize the biological integrity. Hence, SP can be considered as an instantaneous system for defense, stress, healing, etc. SP is known to perform a vital role in neurogenic inflammation and the pathophysiology of acute pancreatitis. Out of these, neurogenic inflammation is responsible for acute interstitial pancreatitis as a result of oedema. SP binds itself to the G-protein coupled neurokinin-1 receptor and causes plasma leakage, cell proliferation, and invasion resulting in pancreatic cancer. SP along with comparable neuropeptides seems to be crucial targets with the capability of satisfying several unfulfilled medical requisites. This review article mainly focuses on compiling the available evidence to show that SP could be a novel therapeutic target for pancreatic diseases, and more exploration into the SP signaling pathways is the call of the hour.

Update on selective treatments targeting neutrophilic inflammation in atherogenesis and atherothrombosis

2014 ◽  
Vol 111 (04) ◽  
pp. 634-646 ◽  
Author(s):  
Ana Luíza Gomes Quinderé ◽  
Norma Maria Barros Benevides ◽  
Federico Carbone ◽  
François Mach ◽  
Nicolas Vuilleumier ◽  
...  
Keyword(s):  
Pathological Process ◽  
Major Adverse Cardiovascular Events ◽  
Plaque Vulnerability ◽  
Potential Therapeutic Target ◽  
Atherosclerotic Burden ◽  
Inflammatory Processes ◽  
Current Therapies ◽  
Thrombotic Complications ◽  
Therapeutic Perspective

SummaryAtherosclerosis is the most common pathological process underlying cardiovascular diseases. Current therapies are largely focused on alleviating hyperlipidaemia and preventing thrombotic complications, but do not completely eliminate risk of suffering recurrent acute ischaemic events. Specifically targeting the inflammatory processes may help to reduce this residual risk of major adverse cardiovascular events in atherosclerotic patients. The involvement of neutrophils in the pathophysiology of atherosclerosis is an emerging field, where evidence for their causal contribution during various stages of atherosclerosis is accumulating. Therefore, the identification of neutrophils as a potential therapeutic target may offer new therapeutic perspective to reduce the current atherosclerotic burden. This narrative review highlights the expanding role of neutrophils in atherogenesis and discusses on the potential treatment targeting neutrophil-related inflammation and associated atherosclerotic plaque vulnerability.

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