1,721,014 research outputs found
5-HT and histamine release from rat basophilic leukemia cells treated or non with IL-1RA
No full textPotential therapeutic use of IL-37: a key suppressor of innate immunity and allergic immune responses mediated by mast cells
No full textThe host response to either exogenous or endogenous insults produces a series of changes, characterized by alterations in immunological functions and generation of mediators called cytokines which include the interleukin-1 (IL-1) family members. IL-1 acts as a hormone mediating the host responses to infection and inflammation. Blocking inflammatory IL-1 family members can be effective against inflammatory disorders, including allergies. IL-37, (formerly IL-1 family member 7), emerges as an inhibitor of innate and adaptive immunity by reducing circulating and organ cytokine levels. IL-37, mainly expressed in dendritic cells, monocytes, and plasma cells after TIR ligand activation, inhibits inflammatory cytokines and augments the level of anti-inflammatory IL-10. IL-37 is involved in allergic reaction and its expression in dendritic cells causes tollerogenicity and inhibits inflammatory response. Mast cells (MCs) are ubiquitous in the body, reside in numerous mucosal tissues, and are mediators of allergic reaction, and innate and adaptive immunity. MCs are important regulators of cytokine generation in the course of inflammatory responses and allergy, and are implicated in the pathophysiology of allergic asthma. Cysteine protease caspase-1 activation leads to the cleavage of pro-form of IL-1 into active mature IL-1 which is present in stimulated and unstimulated inflammatory MCs. Inflammatory cytokine inhibition, along with the augmentation of anti-inflammatory IL-10 by IL-37, is certainly beneficial and improves the pathogenesis of allergic disorders. However, in these studies, the exact mechanism(s) of IL-37-induced anti-inflammatory and anti-allergic activity along with its side effect(s) remain to be determined
Link between mast cells and bacteria: Antimicrobial defense, function and regulation by cytokines
No full textBacteria and their products, such as LPS, act on mast cells (MCs) to induce the secretion of multiple cytokines, including IL-1, TNF, IL-18 and IL-33, which can be dosed in the site of infected tissues. Antigen-binding IgE cross-links FcεRI on mast cells involves the generation and activation of PKCδ, ERK, tyrosine kinases (Syk and Lyn) and mitogen-activated protein kinases (MAPKs), inducing the release of chemical mediators which provoke inflammation and hypersensitive reaction. Other stimuli, including, cytokines, neuropeptides, chemical and physical activators, can also act on MCs to release a plethora of inflammatory compounds. Activated MCs produce a broad spectrum of inflammatory cytokines, chemokines, lipid compounds and vasoactive amines, all involved in immune response. By producing TNF, MCs have an antibacterial defense and a protective function; while pathogenic bacteria and their products, such as LPS, have an inflammatory response through MC activation. LPS binding TLR4 produce MC generation IL-1 family members, and chemokines, which may recruit inflammatory cells at the infection site; whereas in KitW/W-v mice, where MCs are genetically absent, the inflammatory effect is not present. We report for the first time a link between MCs and bacteria emphasizing the mediation of inflammatory cytokines/chemokines. We can conclude that mast cells fight bacteria, and their immune response is perfectly integrated in the immune network. We hope that the understanding of microbial and mast cell interaction leads to more efficient therapeutic development in relation to microbial resistance
Impact of mast cells in mucosal immunity of intestinal inflammation: Inhibitory effect of IL-37
No full textMast cells (MCs) are implicated in an array of diseases, especially those involving a mucosal surface, including intestine. On appropriate activation from cytoplasmatic granules, MCs release preformed chemical mediators and generate inflammatory lipids and cytokines/chemokines. Intracellular signal and Lyn activation pathways can cause the degranulation of MCs and the generation of lipid mediators and cytokines/chemokines. MCs undergo maturation and polarization in gut mucosal surfaces where they are constitutively present, and can alter intestinal permeability, an important factor in many inflammatory mucosal disorders including autoimmune diseases. On the other hand, since they are immununosuppressive, MCs have potential anti-inflammatory properties by producing TGF-Î21, interleukin (IL)-4, IL-10, IL-13 and histamine. In addition, MC chymase, located in the sub-mucosa, acts on intestinal permeability by protecting the bowel. To carry the inflammatory response, MCs need to be attracted by CC chemokines such as RANTES (CCL5) and MCP-1(CCL2), an effect absent in genetically W/Wvmast cell-deficient mice, where the inflammatory reaction is not present. Here, we focused our attention on recent findings regarding how MCs can initiate and develop the cellular immune response in the gut and mediate inflammation, an effect that can be inhibited by IL-37. These studies contribute to clarify the mechanisms by which MCs profoundly affect immunity and inflammation of the intestine
Migraine Headaches: The Immunologist's View
Full text linkObjective: Review evidence supporting the role of mast cells in migraine pathophysiology.Background: Mast cells are known for their role in allergic reactions, but they are also important in immunity and inflammatory diseases, especially those precipitated or worsened by stress. Such are migraine headaches that are associated with spreading neuronal depression and neurogenic inflammation intracranially. Migraines are also comorbid with allergies and could precipitate acute coronary syndromes (ACS). Mast cells are located perivascularly, in close association with neurons, especially in the meninges. Mast cells can be activated by trigeminal nerve stimulation and by acute stress, leading to increased vascular permeability and neurogenic inflammation dependent on NK-1 receptors, but not necessarily on substance P (SP). Methods: We reviewed relevant literature and summarized our own findings.Results: Corticotropin-releasing hormone (CRH), a mediator of the stress response released from the hypothalamus, can activate CRH receptors either on the sensory nuclei of the trigeminal nerve or directly on the mast cells. They, then release proinflammatory, nociceptive and vasoactive mediators including histamine, tryptase and vascular endothelial growth factor (VEGF), thereby triggering migraine headaches.  Conclusions: These results indicate that there are several novel points of intervention for the development of therapeutic agents to help alleviate migraines. Preliminary clinical studies with brain mast cell blockers and CRH receptor antagonists suggest that they could be useful prophylactically
Mast cells participate in allograft rejection: can IL-37 play an inhibitory role?
No full textObjective: The aim of this study was to evaluate the role of mast cells (MCs) in allograft rejection, eventually inhibited by IL-37. Immune cells including MCs participate in allograft rejection by generating IL-1, IL-33, TNF and other cytokines. Methods: We evaluated allograft rejection on the experience of our experimental data and using the relevant literature. Results: MCs are involved in initiation and regulation of innate and adaptive immune responses-pathways. MCs are important pro-inflammatory cells which express high-affinity receptor FceRI and can be activated by IgE and some pro-inflammatory cytokines, such as IL-1 and IL-33. The cross-linkage of high affinity IgE receptor on MCs by antigen ligation has a crucial role in allergy, asthma, anaphylaxis, cancer and allograft rejection. MCs mediate immunity in organ transplant, leading to the activation of allospecific T cells implicated in the rejection and generate pro-inflammatory cytokines/chemokines. IL-1 pro-inflammatory cytokine family members released by MCs mediate allograft rejection and inflammation. IL-37 is also an IL-1 family member generated by macrophage cell line in small amounts, which binds to IL-18Rα and produces an anti-inflammatory effect. IL-37 provokes the inhibition of TLR signaling, TLR-induced mTOR and (MyD88)-mediated responses, suppressing pro-inflammatory IL-1 family members and increasing IL-10. Conclusion: IL-37 inhibition offers the opportunity to immunologically modulate MCs, by suppressing their production of IL-1 family members and reducing the risk of allograft rejection, resulting as a potential good therapeutic new cytokine. Here, we report the relationship between inflammatory MCs, allograft rejection and pro-inflammatory and anti-inflammatory IL-37
Mast cell activation and autism
No full textAbstractAutism spectrum disorders (ASD) are neurodevelopmental disorders characterized by varying degrees of dysfunctional communication and social interactions, repetitive and stereotypic behaviors, as well as learning and sensory deficits. Despite the impressive rise in the prevalence of autism during the last two decades, there are few if any clues for its pathogenesis, early detection or treatment. Increasing evidence indicates high brain expression of pro-inflammatory cytokines and the presence of circulating antibodies against brain proteins. A number of papers, mostly based on parental reporting on their children's health problems, suggest that ASD children may present with “allergic-like” problems in the absence of elevated serum IgE and chronic urticaria. These findings suggest non-allergic mast cell activation, probably in response to environmental and stress triggers that could contribute to inflammation. In utero inflammation can lead to preterm labor and has itself been strongly associated with adverse neurodevelopmental outcomes. Premature babies have about four times higher risk of developing ASD and are also more vulnerable to infections, while delayed development of their gut–blood–brain barriers makes exposure to potential neurotoxins likely. Perinatal mast cell activation by infectious, stress-related, environmental or allergic triggers can lead to release of pro-inflammatory and neurotoxic molecules, thus contributing to brain inflammation and ASD pathogenesis, at least in a subgroup of ASD patients. This article is part of a Special Issue entitled: Mast cells in inflammation
Impact of mast cells in depression disorder: inhibitory effect of IL-37 (new frontiers)
No full textThe purpose of this article is to study the involvement of inflammatory mast cells (MCs) in depression which may be inhibited by IL-37. We evaluate mast cells in depression on the basis of our previous experimental data, and using the most relevant studies reported in the literature. Dysfunction of mood, feelings, and thoughts is a major risk factor for several metabolic diseases and may influence the physiology of the body leading to depression. Depression, present in mastocytosis, is an important endogenous process that promotes the activation of meningeal cell receptors through a low-grade neurogenic chronic inflammation, and MCs. Mast cells are localized along meningeal blood vessels and connective tissues, as well as between the ganglion cells and nerve fibers. They are present in the hypothalamus of mammalian brains capable of communication with nerves. MCs are classically activated by binding to IgE cross-link FcεRI high-affinity receptor leading to release a plethora of mediators responsible for the generation of inflammatory cytokines. Corticotropin-releasing hormone (CRH), produced by MCs, has been found in microglial cells where it regulates immune cells and contributes to the pathogenesis of neurodegenerative diseases including depression. Inflammatory cytokines released by MCs aggravate depression and could be partially inhibited by IL-37. A detailed understanding of the interaction between the immune system, including MCs and depression, is necessary in order to address an effective therapy which could include IL-37. As a consequence, the concepts reviewed here have treatment implications
Role of mast cells in tumor growth
No full textThe growth of malignant tumors is determined in large part by the proliferative capacity of the tumor cells. Clinical observations and animal experiments have established that tumor cells elicit immune responses. Histopathologic studies show that many tumors are surrounded by mononuclear cell and mast cell infiltrates. Mast cells are ubiquitous in the body and are critical for allergic reactions. Increasing evidence indicates that mast cells secrete proinflammatory cytokines and are involved in neuro-inflammatory processes and cancer. Mast cells accumulate in the stroma surrounding certain tumors, especially mammary adenocarcinoma, and the molecules they secrete can benefit the tumor. However, mast cells can also increase at the site of tumor growth and participate in tumor rejection. Mast cells may be recruited by tumor-derived chemoattractants and selectively secrete molecules such as growth factors, histamine, heparin, VEGF, and IL-8, as well as proteases that permit the formation of new blood vessels and metastases. Tumor mast cell intersections play regulatory and modulatory roles affecting various aspects of tumor growth. Discovery of these new roles of mast cells further complicates the understanding of tumor growth. This review focuses on the strategic importance of mast cells to the progression of tumors, and proposes a revised immune effector mechanism of mast cell involvement in tumor growth
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