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Damage-associated molecular patterns (DAMPs) are endogenous danger molecules that are released from damaged or dying cells and activate the innate immune system by interacting with pattern recognition receptors (PRRs). Although DAMPs contribute to the host's defense, they promote pathological inflammatory responses. Recent studies have suggested th...
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... are important components of the innate immune system. Several families of PRRs have been identified in the diverse compartments of the cell ( Table 2). They recognize microbes or tissue damage by specific molecular structures called pathogen-associated molecular patterns (PAMPs) or DAMPs (10,22). ...
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Citations
... Damage-Associated Molecular Patterns (DAMPs) have a controversial role in cancer [61]. DAMPs can either prevent the growth of tumours by immunogenic cell death (ICD) or mediate the advancement of tumours by causing persistent inflammation. ...
Opinion Statement
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... The delayed onset of MIS-C after the initial infection may be due to evolving host immune responses to the products of damaged cells and not the virus itself. Since SARS-CoV-2 leads to the damage of cells in multiple organs, it may give rise to damage-associated molecular patterns (DAMPs), which induce the production of inflammatory cytokines and chemokines [18,19]. In this context, we hypothesized that children who progress to MIS-C develop a stereotypical type of T helper-cell inflammatory response, which in turn elicits the release of DAMPs and induction of harmful autoantibodies (autoAbs). ...
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... DAMPs, which are structurally and functionally diverse, are not caused by pathogenic infections directly but instead by noninfectious physical, chemical, or metabolic agents, and are thus described as "sterile" because they are noninfectious (Behnia et al. 2016). DAMPs signal that cells have been damaged and so play key roles in signaling to the innate immune system that something is wrong with the body itself and that inflammatory activity needs to be increased (Roh and Sohn 2018). Elevation in inflammatory activity is meant to be short term, however, and is intended to be downregulated in response to anti-inflammatory signals once the threat is resolved (McDade 2023). ...
This article examines the relationship between social inequity and the immune system, emphasizing some of the many ways that systemic racism and other forms of marginalization can undermine health. Of much sociological con- cern, chronic stressors increase inflammation and consequent susceptibility to health morbidities and, ultimately, mortality by burdening marginalized group members in ways that adversely affect immune regulation and functioning. As with social sys- tems more generally, the immune system is a cross-scale complex system of many regulating, coordinating, and interacting parts, within both itself and the other bodily systems it protects. Along these lines, we thus propose that to properly conceptualize how social conditions undermine immune functioning and health, it is important to consider the immune system beyond its component mechanisms and parts. This view is akin to the way critical race theory proposes that “systemic racism” in the United States is a collaborative arrangement of social structures whose explanatory richness and historical durability can only be fully understood as a gestalt. We therefore seek, where possible, to emphasize the systems nature of the immune system similarly to the sociological insight that society comprises complex systems whose interrelated structures interact in dynamic and sometimes unpredictable ways. We scaffold this discussion within the literature on systemic racism in the United States, emphasizing inflammation as a key marker of immune demand and dysregulation and highlight- ing some implications for health inequities among marginalized populations more generally.
... DAMPs, which are structurally and functionally diverse, are not caused by pathogenic infections directly but instead by noninfectious physical, chemical, or metabolic agents, and are thus described as "sterile" because they are noninfectious (Behnia et al. 2016). DAMPs signal that cells have been damaged and so play key roles in signaling to the innate immune system that something is wrong with the body itself and that inflammatory activity needs to be increased (Roh and Sohn 2018). Elevation in inflammatory activity is meant to be short term, however, and is intended to be downregulated in response to anti-inflammatory signals once the threat is resolved (McDade 2023). ...
This article examines the relationship between social inequity and the immune system, emphasizing some of the many ways that systemic racism and other forms of marginalization can undermine health. Of much sociological concern, chronic stressors increase inflammation and consequent susceptibility to health morbidities and, ultimately, mortality by burdening marginalized group members in ways that adversely affect immune regulation and functioning. As with social systems more generally, the immune system is a cross-scale complex system of many regulating, coordinating, and interacting parts, within both itself and the other bodily systems it protects. Along these lines, we thus propose that to properly conceptualize how social conditions undermine immune functioning and health, it is important to consider the immune system beyond its component mechanisms and parts. This view is akin to the way critical race theory proposes that “systemic racism” in the United States is a collaborative arrangement of social structures whose explanatory richness and historical durability can only be fully understood as a gestalt. We therefore seek, where possible, to emphasize the systems nature of the immune system similarly to the sociological insight that society comprises complex systems whose interrelated structures interact in dynamic and sometimes unpredictable ways. We scaffold this discussion within the literature on systemic racism in the United States, emphasizing inflammation as a key marker of immune demand and dysregulation and highlighting some implications for health inequities among marginalized populations more generally.
... There exists a certain relationship between atherosclerosis and heat shock proteins (HSPs) [5]. Heat shock proteins are a group of proteins produced in cells in response to stress or damage and are involved in cellular protection and repair processes. ...
Clinical evidence suggests anti-Hsp60 antibodies could contribute to atherosclerosis (AS) development, with unclear mechanisms. This study aims to explore the role of anti-HSP60-mediated autoimmunity in AS progression. HSP60-MHC tetramers were used to characterize HSP60-specific CD4 + T cells and assess TCR responses in mice. These cells were transplanted into AS mice to examine immune cell differentiation and infiltration in plaques and blood. Mice were injected with recombinant HSP60 or anti-HSP60 sera to evaluate effects on plaque progression and macrophage activity. Experiments with muMT–/–Apoe–/– mice examined humoral immunity's role in this autoimmunity. HSP60-reactive CD4 + T cells in AS mice differentiated into follicular helper cells, not Th1/Th17. Anti-HSP60 treatments increased macrophage infiltration and M1 polarization, indicating an anti-HSP60-driven inflammatory progression, dependent on humoral immunity. Anti-HSP60 influences macrophage infiltration, polarization, and plaque formation via humoral immunity, shedding light on its potential role in AS progression.
Graphical Abstract
... In this case, reorganization of cytoskeleton can occur through direct oxidation and disruption of the cytoskeleton proteins leading to structural changes, or through inhibition of actin polymerization by interference with the signaling pathways involved in this process (Mittal et al., 2014). Infection-free (sterile) inflammation occurs when immune cells recognize damage-related molecular patterns (DAMPs) as antigens (Roh and Sohn, 2018). DAMPs are endogenous danger molecules that are secreted from damaged cells and stimulate the innate immune system by interacting with pattern recognition receptors. ...
... Consequently, a positive feedback loop may form, promoting inflammation to persist and, ultimately, chronic inflammation. ROS contribute to this process by modifying DAMPs by oxidation, which increases their immunogenicity (Roh and Sohn, 2018). Therefore, ROS are directly involved in the initiation of inflammation and its subsequent chronification, which can occur when acute inflammation fails to resolve. ...
The excessive production of various reactive oxidant species over endogenous antioxidant defense mechanisms leads to the development of a state of oxidative stress, with serious biological consequences. The consequences of oxidative stress depend on the balance between the generation of reactive oxidant species and the antioxidant defense and include oxidative damage of biomolecules, disruption of signal transduction, mutation, and cell apoptosis. Accumulating evidence suggests that oxidative stress is involved in the physiopathology of various debilitating illnesses associated with chronic inflammation, including cardiovascular diseases, diabetes, cancer, or neurodegenerative processes, that need continuous pharmacological treatment. Oxidative stress and chronic inflammation are tightly linked pathophysiological processes, one of which can be simply promoted by another. Although, many antioxidant trials have been unsuccessful (some of the trials showed either no effect or even harmful effects) in human patients as a preventive or curative measure, targeting oxidative stress remains an interesting therapeutic approach for the development of new agents to design novel anti-inflammatory drugs with a reliable safety profile. In this regard, several natural antioxidant compounds were explored as potential therapeutic options for the treatment of chronic inflammatory diseases. Several metalloenzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, are among the essential enzymes that maintain the low nanomolar physiological concentrations of superoxide (O2•−) and hydrogen peroxide (H2O2), the major redox signaling molecules, and thus play important roles in the alteration of the redox homeostasis. These enzymes have become a striking source of motivation to design catalytic drugs to enhance the action of these enzymes under pathological conditions related to chronic inflammation. This review is focused on several major representatives of natural and synthetic antioxidants as potential drug candidates for the treatment of chronic inflammatory diseases.
... Moreover, reliable evidence suggests that Damage Associated Molecular Pattern (DAMP)-induced inflammation plays an important role in the pathogenesis of OA. FN-1, as a DAMP molecule, can induce activation of a toll-like receptor 4 (TLR4) and promote the release of inflammatory factors [24]. Therefore, to uncover the possible reason that DSPP haplodeficency led to TMJ OA, we observed the alteration of FN-1 and TLR-4 in MCC, data showed both molecules markedly increased in MCC (Fig. 5j-k, j'-k' , l-m, l'-m'). ...
Background
Extracellular matrix (ECM) protein malfunction or defect may lead to temporomandibular joint osteoarthritis (TMJ OA). Dentin sialophophoprotein (DSPP) is a mandibular condylar cartilage ECM protein, and its deletion impacted cell proliferation and other extracellular matrix alterations of postnatal condylar cartilage. However, it remains unclear if long-term loss of function of DSPP leads to TMJ OA. The study aimed to test the hypothesis that long-term haploinsufficiency of DSPP causes TMJ OA.
Materials and methods
To determine whether Dspp+/– mice exhibit TMJ OA but no severe tooth defects, mandibles of wild-type (WT), Dspp+/–, and Dspp homozygous (Dspp−/−) mice were analyzed by Micro-computed tomography (micro-CT). To characterize the progression and possible mechanisms of osteoarthritic degeneration over time in Dspp+/– mice over time, condyles of Dspp+/– and WT mice were analyzed radiologically, histologically, and immunohistochemically.
Results
Micro-CT and histomorphometric analyses revealed that Dspp+/– and Dspp−/− mice had significantly lower subchondral bone mass, bone volume fraction, bone mineral density, and trabecular thickness compared to WT mice at 12 months. Interestingly, in contrast to Dspp−/− mice which exhibited tooth loss, Dspp+/– mice had minor tooth defects. RNA sequencing data showed that haplodeficency of DSPP affects the biological process of ossification and osteoclast differentiation. Additionally, histological analysis showed that Dspp+/– mice had condylar cartilage fissures, reduced cartilage thickness, decreased articular cell numbers and severe subchondral bone cavities, and with signs that were exaggerated with age. Radiographic data showed an increase in subchondral osteoporosis up to 18 months and osteophyte formation at 21 months. Moreover, Dspp+/– mice showed increased distribution of osteoclasts in the subchondral bone and increased expression of MMP2, IL-6, FN-1, and TLR4 in the mandibular condylar cartilage.
Conclusions
Dspp+/– mice exhibit TMJ OA in a time-dependent manner, with lesions in the mandibular condyle attributed to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers.
... They can be classified as protein damage-associated molecular patterns, such as heat shock proteins, histones, high-mobility group box 1 protein (HMGB1), and S100 molecules, or nonprotein damage-associated molecular patterns, including DNA and RNA. Recognition of alarmins is primarily mediated by the NLRP3 inflammasome, which regulates the release of IL-1b and IL-18 (Nürnberger and Kemmerling, 2009;Roh and Sohn, 2018;Relja and Land, 2020). ...
Infectious diseases are among the factors that account for a significant proportion of disease-related deaths worldwide. The primary treatment approach to combat microbial infections is the use of antibiotics. However, the widespread use of these drugs over the past two decades has led to the emergence of resistant microbial species, making the control of microbial infections a serious challenge. One of the most important solutions in the field of combating infectious diseases is the regulation of the host’s defense system. Toll-like receptors (TLRs) play a crucial role in the first primary defense against pathogens by identifying harmful endogenous molecules released from dying cells and damaged tissues as well as invading microbial agents. Therefore, they play an important role in communicating and regulating innate and adaptive immunity. Of course, excessive activation of TLRs can lead to disruption of immune homeostasis and increase the risk of inflammatory reactions. Targeting TLR signaling pathways has emerged as a new therapeutic approach for infectious diseases based on host-directed therapy (HDT). In recent years, stem cell-derived exosomes have received significant attention as factors regulating the immune system. The regulation effects of exosomes on the immune system are based on the HDT strategy, which is due to their cargoes. In general, the mechanism of action of stem cell-derived exosomes in HDT is by regulating and modulating immunity, promoting tissue regeneration, and reducing host toxicity. One of their most important cargoes is microRNAs, which have been shown to play a significant role in regulating immunity through TLRs. This review investigates the therapeutic properties of stem cell-derived exosomes in combating infections through the interaction between exosomal microRNAs and Toll-like receptors.
... A recent study demonstrated that NP is correlated with the upregulation of genes that encode key regulators of inflammatory cascades, including pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) [19]. TLRs represent the primary and earliest recognition mechanism for pathogen-associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs), leading to the subsequent activation of the inflammatory cascade [20][21][22]. Among TLRs, several (TLR1, TLR2, TLR3, TLR5, TLR7, and TLR8) were significantly upregulated in the chorioallantois of NP cases [19], suggesting that microorganisms may be responsible for initiating the inflammatory cascade. ...
... The host innate immune response is the body's first line of defense against pathogens [1,2]. Human innate immune receptors recognize conserved signatures on pathogens known as pathogen associated molecular patterns (PAMPs), which are important signaling molecules released by pathogens during infection [3,4]. These molecules bind host cell pattern recognition receptors (PRRs) typically found on endothelial, epithelial, or tissue-resident immune cells such as macrophages and dendritic cells triggering a signal cascade that upregulates expression of cytokines and chemokines. ...
Universal and early recognition of pathogens occurs through recognition of evolutionarily conserved pathogen associated molecular patterns (PAMPs) by innate immune receptors and the consequent secretion of cytokines and chemokines. The intrinsic complexity of innate immune signaling and associated signal transduction challenges our ability to obtain physiologically relevant, reproducible and accurate data from experimental systems. One of the reasons for the discrepancy in observed data is the choice of measurement strategy. Immune signaling is regulated by the interplay between pathogen-derived molecules with host cells resulting in cellular expression changes. However, these cellular processes are often studied by the independent assessment of either the transcriptome or the proteome. Correlation between transcription and protein analysis is lacking in a variety of studies. In order to methodically evaluate the correlation between transcription and protein expression profiles associated with innate immune signaling, we measured cytokine and chemokine levels following exposure of human cells to the PAMP lipopolysaccharide (LPS) from the Gram-negative pathogen Pseudomonas aeruginosa . Expression of 84 messenger RNA (mRNA) transcripts and 69 proteins, including 35 overlapping targets, were measured in human lung epithelial cells. We evaluated 50 biological replicates to determine reproducibility of outcomes. Following pairwise normalization, 16 mRNA transcripts and 6 proteins were significantly upregulated following LPS exposure, while only five (CCL2, CSF3, CXCL5, CXCL8/IL8, and IL6) were upregulated in both transcriptomic and proteomic analysis. This lack of correlation between transcription and protein expression data may contribute to the discrepancy in the immune profiles reported in various studies. The use of multiomic assessments to achieve a systems-level understanding of immune signaling processes can result in the identification of host biomarker profiles for a variety of infectious diseases and facilitate countermeasure design and development.
