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Postnatal supplementation with alarmins S100a8/a9 ameliorates malnutrition-induced neonate enteropathy in mice.

Malnutrition is linked to 45% of global childhood mortality, however, the impact of maternal malnutrition on the child's health remains elusive. Previous studies suggested that maternal malnutrition does not affect breast milk composition. Yet, malnourished children often develop a so-called environmental enteropathy, assumed to be triggered by frequent pathogen uptake and unfavorable gut colonization. Here, we show in a murine model that maternal malnutrition induces a persistent inflammatory gut dysfunction in the offspring that establishes during nursing and does not recover after weaning o

Hepatic Alarmins and Mitochondrial Dysfunction under Residual Hyperlipidemic Stress Lead to Irreversible NAFLD.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) includes a range of progressive disorders generated by excess lipid accumulati … the interruption of the hypercholesterolemic diet to identify also the potential mediators, such as alarmins, responsible for the irreversible NAFLD build up under the hyperlipidemic sustained stress. RESULTS: Proteomic analysis revealed a number of proteins whose abundance was altered. They were components of metabolic pathways including fatty-acid degra …

A metabolic alarmin from keratinocytes potentiates systemic humoral immunity.

How a local infection triggers systemic humoral immunity remains unclear. Here we identify farnesyl pyrophosphate (FPP), a mevalonate pathway metabolic intermediate1, as an endogenous alarmin that enhances IgG antibody responses through keratinocyte-derived IL-6 and CCL20. This signalling axis potentiates the differentiation of T follicular helper cells and migratory dendritic cells2,3. FPP accumulates within keratinocytes after infection or ultraviolet irradiation through the activation of the mevalonate pathway mediated by the unfolded protein response-SREBF pathway, amplifying germinal cent

The Emerging Role of Alarmin-Targeting Biologics in the Treatment of Patients With COPD.

TOPIC IMPORTANCE: COPD is a complex, heterogeneous lung disease characterized by persistent airflow limitation secondary to airways and pare … alone may be insufficient to treat COPD. Based on a better understanding of the disease and role of alarmins, with a broader role in the inflammatory cascade, it is likely that some biologics may benefit certain COPD endotypes. Ongoing trials will provide information about which groups can benefit from the blocking of specific pathways (eg, IL-5, IL-4/IL-1 …

Alarmin(g) the innate immune system to invasive fungal infections.

Fungi encounter numerous stresses in a mammalian host, including the immune system, which they must adapt to in order to grow and cause disease. The host immune system tunes its response to the threat level posed by the invading pathogen. We discuss recent findings on how interleukin (IL)-1 signaling is central to tuning the immune response to the virulence potential of invasive fungi, as well as other pathogens. Moreover, we discuss fungal factors that may drive tissue invasion and destruction that regulate IL-1 cytokine release. Moving forward understanding the mechanisms of fungal adaption

NSE and S100β as serum alarmins in predicting neurological outcomes after cardiac arrest.

Cardiac arrest (CA) is a serious health concern that often results in mortality or severe neurological dysfunction in the case of survival. Our aim was to explore the neurological prognostic factors in patients with CA. This retrospective observational study included adult patients with CA. We investigated serum neuron-specific enolase (NSE), S100 calcium-binding protein β (S100β), and indices and parameters at 1, 3, 5, 7 and intensive care unit (ICU) discharge days after CA. The primary study endpoint was the Cerebral Performance Category (CPC) scale score at ICU discharge, which was dichotom

Serum alarmins and the risk of incident interstitial lung disease in rheumatoid arthritis.

OBJECTIVES: To quantify associations of serum alarmins with risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: Using serum collected at enrolment, three alarmins (IL-33, thymic stromal lymphopoietin [TSLP] and IL-25) were measured in a multicentre prospective RA cohort. ILD was classified using systematic medical record review. Cross-sectional associations of log-transformed (IL-33, TSLP) or quartile (IL-25) values with RA-ILD at enrolment (prevalent RA-ILD) were examined using logistic regression, while associations with incident RA-ILD developing after enro…

Role of Damage-Associated Molecular Patterns (DAMPs/Alarmins) in Severe Ocular Allergic Diseases.

Severe ocular allergic diseases, such as atopic keratoconjunctivitis and vernal keratoconjunctivitis, cause severe allergic inflammation in the conjunctiva and corneal epithelial damage, resulting in visual disturbances. The involvement of damage (danger)-associated molecular patterns (DAMPs/alarmins) in the pathogenesis of these diseases has been recognized. Alarmins released from damaged corneal epithelial cells or eosinophils play a critical role in the induction of corneal lesions, vicious loop of corneal injury, and exacerbation of conjunctival allergic inflammation. Alarmins in the conju…

Alarmins in Osteoporosis, RAGE, IL-1, and IL-33 Pathways: A Literature Review.

Alarmins are endogenous mediators released by cells following insults or cell death to alert the host's innate immune system of a situation of danger or harm. Many of these, such as high-mobility group box-1 and 2 (HMGB1, HMGB2) and S100 (calgranulin proteins), act through RAGE (receptor for advanced glycation end products), whereas the IL-1 and IL-33 cytokines bind the IL-1 receptors type I and II, and the cellular receptor ST2, respectively. The alarmin family and their signal pathways share many similarities of cellular and tissue localization, functions, and involvement in various physiolo…

Alarmins from corneal epithelial cells upregulate CCL11 and VCAM-1 in corneal fibroblasts.

PURPOSE: Severe ocular allergic diseases are characterized by pronounced conjunctival inflammation triggered by T helper 2 (Th2) cells and corneal epithelial damage induced by eosinophils. To examine the role of alarmins released by damaged corneal epithelial cells in tissue eosinophilia, we investigated the effects of a supernatant derived from necrotic human corneal epithelial (HCE) cells on expression of the chemokine CCL11 (eotaxin) and the adhesion molecule VCAM-1 in human corneal fibroblasts. METHODS: An alarmin preparation was obtained as the material released from HCE cells after thre…

Внеклеточные нуклеотиды являются посредником в вирусных инфекциях центральной нервной системы: ключи от нейроинфламмации и нейродегенерации.

Недавний рост инфекционных заболеваний, затрагивающих центральную нервную систему, вызвал обеспокоенность по поводу их роли в нейроинфламмации и нейродегенерации. Вирусные патогены или их продукты могут вторгаться в центральную нервную систему и вызывать повреждения, ведущие к менингиту, энцефалиту, менингоэнцефалиту, миелиту или постинфекционным демиелинизирующим заболеваниям. Хотя изначально нейроинфламмация имеет защитную функцию, хроническое воспаление может способствовать развитию нейродегенеративных заболеваний. Такие механизмы, как агрегация белков и клеточные расстройства, связаны с ко

Совпадение в аннотации оригинала
Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and … triphosphate and its metabolites are released from activated, infected, and dying cells, acting as alarmins mediating neuroinflammation and neurodegeneration. When viruses infect central nervous system cells, adenosine triphosphate is released as an alarmin, triggering inflammatory responses. This process is mediated by purinergic receptors, divided into …

Therapeutic monoclonal antibodies in allergy: Targeting IgE, cytokine, and alarmin pathways.

The etiology of allergy is closely linked to type 2 inflammatory responses ultimately leading to the production of allergen-specific immunoglobulin E (IgE), a key driver of many allergic conditions. At a high level, initial allergen exposure disrupts epithelial integrity, triggering local inflammation via alarmins including IL-25, IL-33, and TSLP, which activate type 2 innate lymphoid cells as well as other immune cells to secrete type 2 cytokines IL-4, IL-5 and IL-13, promoting Th2 cell development and eosinophil recruitment. Th2 cell dependent B cell activation promotes the production of all…

Alarmins and their pivotal role in the pathogenesis of spontaneous abortion: insights for therapeutic intervention.

Alarmins are a class of molecules released when affected cells damaged or undergo apoptosis. They contain various chemotactic and immunomodulatory proteins or peptides. These molecules regulate the immune response by interacting with pattern recognition receptors (PRRs) and play important roles in inflammatory response, tissue repair, infection defense, and cancer treatment. Spontaneous abortion (SA) is a common pregnancy-related disease, and its pathogenesis has been puzzling clinicians, so it needs to be further studied. In this paper, we first reviewed the research status of various alarmin…

Alarmin S100A11 initiates a chemokine response to the human pathogen Toxoplasma gondii.

Toxoplasma gondii is a common protozoan parasite that infects up to one third of the world's population. Notably, very little is known about innate immune sensing mechanisms for this obligate intracellular parasite by human cells. Here, by applying an unbiased biochemical screening approach, we show that human monocytes recognized the presence of T. gondii infection by detecting the alarmin S100A11 protein, which is released from parasite-infected cells via caspase-1-dependent mechanisms. S100A11 induced a potent chemokine response to T. gondii by engaging its receptor RAGE, and regulated mono

Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity.

Inflammation has a key role in the pathogenesis of various human diseases. The early detection, localization and monitoring of inflammation are crucial for tailoring individual therapies. However, reliable biomarkers to detect local inflammatory activities and to predict disease outcome are still missing. Alarmins, which are locally released during cellular stress, are early amplifiers of inflammation. Here, using optical molecular imaging, we demonstrate that the alarmin S100A8/S100A9 serves as a sensitive local and systemic marker for the detection of even sub-clinical disease activity in in…

S100A alarmins and thymic stromal lymphopoietin (TSLP) regulation in severe asthma following bronchial thermoplasty.

RATIONALE: Severe asthma affects a small proportion of asthmatics but represents a significant healthcare challenge. Bronchial thermoplasty (BT) is an interventional treatment approach preconized for uncontrolled severe asthma after considering biologics therapy. It was showed that BT long-lastingly improves asthma control. These improvements seem to be related to the ability of BT to reduce airway smooth muscle remodeling, reduce the number of nerve fibers and to modulate bronchial epithelium integrity and behavior. Current evidence suggest that BT downregulates epithelial mucins expression,

Differential gene expression in drug hypersensitivity reactions: induction of alarmins in severe bullous diseases.

BACKGROUND: Delayed hypersensitivity reactions to drugs can be life-threatening and constitute a growing problem in clinical practice. Altho … ry-related mediators among which several endogenous damage-associated molecular patterns (DAMPs) or alarmins were found. CONCLUSIONS: Distinct gene expression profiles in PMBCs define benign and severe clinical entities. Overexpression of endogenous DAMPs in Stevens-Johnson syndrome and toxic epidermal necrolysis suggest that drugs can trigger the alarmin …

Gastric alarmin release: A warning signal in the development of gastric mucosal diseases.

Alarmins exist outside cells and are early warning signals to the immune system; as such, alarmin receptors are widely distributed on various immune cells. Alarmins, proinflammatory molecular patterns associated with tissue damage, are usually released into the extracellular space, where they induce immune responses and participate in the damage and repair processes of mucosal diseases.In the stomach, gastric alarmin release has been shown to be involved in gastric mucosal inflammation, antibacterial defense, adaptive immunity, and wound healing; moreover, this release causes damage and result…

The alarmin IL-33 promotes regulatory T-cell function in the intestine.

FOXP3(+) regulatory T cells (Treg cells) are abundant in the intestine, where they prevent dysregulated inflammatory responses to self and environmental stimuli. It is now appreciated that Treg cells acquire tissue-specific adaptations that facilitate their survival and function; however, key host factors controlling the Treg response in the intestine are poorly understood. The interleukin (IL)-1 family member IL-33 is constitutively expressed in epithelial cells at barrier sites, where it functions as an endogenous danger signal, or alarmin, in response to tissue damage. Recent studies in hum