Myelin debris regulates inflammatory responses in an experimental demyelination animal model and multiple sclerosis lesions

Abstract Background Inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model. Results Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitis-related clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains. Conclusions These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.

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Immunosuppressive and Anti-Inflammatory Effects of Nicotine Administered by Patch in an Animal Model

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.11.3.563-568.2004 ◽

2004 ◽

Vol 11 (3) ◽

pp. 563-568 ◽

Cited By ~ 49

Author(s):

Roma Kalra ◽

Shashi P. Singh ◽

Juan C. Pena-Philippides ◽

Raymond J. Langley ◽

Seddigheh Razani-Boroujerdi ◽

...

Keyword(s):

Animal Model ◽

Immune System ◽

Inflammatory Responses ◽

Nicotine Patch ◽

Subcutaneous Administration ◽

Spleen Cells ◽

Self Administration ◽

Nicotine Administration ◽

Nicotine Patches ◽

Immunological Effects

ABSTRACT To study the immunological effects of nicotine, there are several rodent models for chronic nicotine administration. These models include subcutaneously implanted miniosmotic pumps, nicotine-spiked drinking water, and self-administration via jugular cannulae. Administration of nicotine via these routes affects the immune system. Smokers frequently use nicotine patches to quit smoking, and the immunological effects of nicotine patches are largely unknown. To determine whether the nicotine patch affects the immune system, nicotine patches were affixed daily onto the backs of Lewis rats for 3 to 4 weeks. The patches efficiently raised the levels of nicotine and cotinine in serum and strongly inhibited the antibody-forming cell response of spleen cells to sheep red blood cells. The nicotine patch also suppressed the concanavalin A-induced T-cell proliferation and mobilization of intracellular Ca2+ by spleen cells, as well as the fever response of animals to subcutaneous administration of turpentine. Moreover, immunosuppression was associated with chronic activation of protein tyrosine kinase and phospholipase C-γ1 activities. Thus, in this animal model of nicotine administration, the nicotine patch efficiently raises the levels of nicotine and cotinine in serum and impairs both the immune and inflammatory responses.

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An overview of the α4β1 integrin and the potential therapeutic role of its antagonists

Current Medicinal Chemistry ◽

10.2174/0929867328666210217153609 ◽

2021 ◽

Vol 28 ◽

Author(s):

Elenilze F. B. Ferreira ◽

Luciane B. Silva ◽

Josiane V. Cruz ◽

Pedro H. F. Araújo ◽

Njogu M. Kimani ◽

...

Keyword(s):

Multiple Sclerosis ◽

Monoclonal Antibody ◽

Extracellular Matrix ◽

Inflammatory Responses ◽

Cellular Responses ◽

Tumour Invasion ◽

Potential Therapeutic Role ◽

Integrin Antagonists ◽

Inside Out

: This article presents a simplified view of integrins with emphasis on the α4 (α4β1/VLA-4) integrin. Integrins are heterodimeric proteins expressed on the cell surface of leukocytes that participate in a wide variety of functions, such as survival, growth, differentiation, migration, inflammatory responses, tumour invasion, among others. When the extracellular matrix is degraded or deformed, cells are forced to undergo responsive changes that influence remodelling during physiological and pathological events. Integrins recognize these changes and trigger a series of cellular responses, forming a physical connection between the interior and the outside of the cell. The communication of integrins through the plasma membrane occurs in both directions, from the extracellular to the intracellular (outside-in) and from the intracellular to the extracellular (inside-out). Integrins are valid targets for antibodies and small molecule antagonists. One example is the monoclonal antibody natalizumab, marketed under the name of TYSABRI®, used in the treatment of recurrent multiple sclerosis, which inhibits the adhesion of α4 integrin to its counter-receptor. α4β1 Integrin antagonists are summarized here and their utility as therapeutics discussed.

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AIM2 inflammasome activation in astrocytes occurs during the late phase of EAE

10.1101/2021.10.03.462457 ◽

2021 ◽

Author(s):

William E. Barclay ◽

M. Elizabeth Deerhake ◽

Makoto Inoue ◽

Toshiaki Nonaka ◽

Kengo Nozaki ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Animal Model ◽

Cell Death ◽

Nervous System ◽

Experimental Autoimmune Encephalomyelitis ◽

Inflammasome Activation ◽

Autoimmune Encephalomyelitis ◽

The Central Nervous System ◽

Experimental Autoimmune

ABSTRACTInflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory responses through their effector cytokines, IL-1β and IL-18. Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are such autoimmune conditions influenced by inflammasomes. Despite work investigating inflammasomes during EAE, little remains known concerning the role of inflammasomes in the central nervous system (CNS) during the disease. Here we use multiple genetically modified mouse models to monitor activated inflammasomes in situ based on ASC oligomerization in the spinal cord. Using inflammasome reporter mice, we found heightened inflammasome activation in astrocytes after the disease peak. In contrast, microglia and CNS-infiltrated myeloid cells had few activated inflammasomes in the CNS during EAE. Astrocyte inflammasome activation was dependent on AIM2, but low IL-1β expression and no significant signs of cell death were found in astrocytes during EAE. Thus, the AIM2 inflammasome activation in astrocytes may have a distinct role from traditional inflammasome-mediated inflammation.SIGNIFICANCE STATEMENTInflammasome activation in the peripheral immune system is pathogenic in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, inflammasome activity in the central nervous system (CNS) is largely unexplored. Here, we used genetically modified mice to determine inflammasome activation in the CNS during EAE. Our data indicated heightened AIM2 inflammasome activation in astrocytes after the disease peak. Unexpectedly, neither CNS-infiltrated myeloid cells nor microglia were the primary cells with activated inflammasomes in SC during EAE. Despite AIM2 inflammasome activation, astrocytes did not undergo apparent cell death and produced little of the proinflammatory cytokine, IL-1β, during EAE. This study showed that CNS inflammasome activation occurs during EAE without associating with IL-1β-mediated inflammation.

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