Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histamine can modulate the cytokine network and influence Th1 and Th2 balance and Ab-isotype switching. Thus, pharmacological blockade or genetic deletion of specific histamine receptors has been shown to reduce the severity of experimental autoimmune encephalomyelitis (EAE), a prototypic Th1-mediated disease with similarities to human multiple sclerosis. To study the comprehensive contribution of endogenous histamine to the expression of EAE, we attempted to induce EAE in histidine decarboxylase-deficient mice, which are genetically unable to make histamine. In this study, we show that EAE is significantly more severe in HDC-/-, histamine-deficient mice, with diffuse inflammatory infiltrates, including a prevalent granulocytic component, in the brain and cerebellum. Unlike splenocytes from wild-type mice, splenocytes from HDC-/- mice do not produce histamine in response to the myelin Ag, whereas production of IFN-gamma, TNF, and leptin are increased in HDC-/- splenocytes in comparison to those from wild-type mice. Endogenous histamine thus appears to regulate importantly the autoimmune response against myelin and the expression of EAE, in this model, and to limit immune damage to the CNS. Understanding which receptor(s) for histamine is/are involved in regulating autoimmunity against the CNS might help in the development of new strategies of treatment for EAE and multiple sclerosis.
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PMID:A key regulatory role for histamine in experimental autoimmune encephalomyelitis: disease exacerbation in histidine decarboxylase-deficient mice. 1636 91

Since its discovery in 1910, histamine has been regarded as one of the most important biogenic amines in the medical and biological fields. This article summarizes the information about the role of histamine in allergic situations, atherosclerosis, and autoimmune encephalomyelitis, especially focusing on our study with histidine decarboxylase gene knockout mouse. In the allergic bronchial asthma model, histamine positively controls eosinophilia but not bronchial hypersensitivity. Histamine is proved to be an important substance that controls body temperature and respiration in systemic anaphylaxis but its role in controlling blood pressure is minor. Histamine also plays a role in inducing atherosclerosis in the mouse model. We showed that experimental autoimmune encephalomyelitis (EAE) is significantly more severe in histamine-deficient mice with diffuse inflammatory infiltrates in the brain and cerebellum, including a prevalent granulocytic component. Histamine is mainly produced in mast cells and basophils in hematopoietic cells. We've shown that mast cells not only produce histamine, but also uptake it from the environmental medium and release it by allergic stimulants. The protein used for the plasma transport of histamine in basophils was identified as organic cation transporter (OCT3).
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PMID:Progress in allergy signal research on mast cells: the role of histamine in immunological and cardiovascular disease and the transporting system of histamine in the cell. 1836 91

Induction of T helper 1 (Th1) to Th2 deviation through administration of self- or altered self-peptides holds promise for treatment of autoimmunity. However, administration of self-peptides in models of autoimmunity can result in anaphylactic reactions. Although both IgE and IgG1 antibodies might be involved in the development of anaphylaxis to myelin peptides in experimental autoimmune encephalomyelitis in mice, the effector cells and molecules involved are not fully understood. Here we show that systemic anaphylaxis to the self-antigen myelin oligodendrocyte glycoprotein (MOG) 35-55 can occur in mice lacking mast cells (Kit(W)/Kit(W-v) mice) or histamine (histidine decarboxylase-deficient mice), but is prevented in mice lacking IL-4. Treatment of mice with CV6209, a platelet-activating factor antagonist, slightly reduced the incidence of anaphylaxis to self-MOG35-55 in this model, but more effectively protected mice against anaphylaxis to this peptide when self-MOG35-55 was administered in a different immunization protocol that omitted the use of Bordetella pertussis toxin as an adjuvant at the time of immunization. Thus, anaphylactic reactions to self-MOG can occur in the absence of mast cells or histamine, key elements of the classical IgE-, mast cell-, and histamine-dependent pathway of anaphylaxis.
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PMID:Anaphylaxis to a self-peptide in the absence of mast cells or histamine. 1918 9

Histamine (HA) is a key regulator of experimental allergic encephalomyelitis (EAE), the autoimmune model of multiple sclerosis. HA exerts its effects through four known G-protein-coupled receptors: H1, H2, H3, and H4 (histamine receptors; H(1-4)R). Using HR-deficient mice, our laboratory has demonstrated that H1R, H2R, H3R, and H4R play important roles in EAE pathogenesis, by regulating encephalitogenic T cell responses, cytokine production by APCs, blood-brain barrier permeability, and T regulatory cell activity, respectively. Histidine decarboxylase-deficient mice (HDCKO), which lack systemic HA, exhibit more severe EAE and increased Th1 effector cytokine production by splenocytes in response to myelin oligodendrocyte gp35-55. In an inverse approach, we tested the effect of depleting systemic canonical HA signaling on susceptibility to EAE by generating mice lacking all four known G-protein-coupled-HRs (H(1-4)RKO mice). In this article, we report that in contrast to HDCKO mice, H(1-4)RKO mice develop less severe EAE compared with wild-type animals. Furthermore, splenocytes from immunized H(1-4)RKO mice, compared with wild-type mice, produce a lower amount of Th1/Th17 effector cytokines. The opposing results seen between HDCKO and H1-4RKO mice suggest that HA may signal independently of H1-4R and support the existence of an alternative HAergic pathway in regulating EAE resistance. Understanding and exploiting this pathway has the potential to lead to new disease-modifying therapies in multiple sclerosis and other autoimmune and allergic diseases.
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PMID:Systemic lack of canonical histamine receptor signaling results in increased resistance to autoimmune encephalomyelitis. 2377 30