Gene/Protein
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Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Drug
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Target Concepts:
Gene/Protein
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Query: UMLS:C0409974 (
lupus
)
22,386
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The autoimmune manifestations of MRL/Mp-lpr/lpr(MRL/l), a murine model of systemic lupus erythematosus (SLE), were alleviated by administering 1 microgram
cholera
toxin (CT) every 14 days. The beneficial effects were: (i) significant prolongation of survival time, (ii) prevention of lymphadenopathy, (iii) improvement of T cell mitogenic responses and suppression of a B cell mitogenic response, (iv) decrease in serum anti-DNA and anti-Sm antibodies, (v) increase in IL-2 production by stimulation of spleen cells with concanavalin A (Con A). It is possible that CT may be effective for treatment of murine lupus nephritis by modulating polyclonal lymphocyte activation. This type of immunomodulation may pave the way toward treatment of
lupus
and other autoimmune diseases.
...
PMID:Treatment of autoimmune MRL/Mp-lpr/lpr mice with cholera toxin. 350 Aug 17
Infectious agents, including bacteria and viruses, are thought to provide triggers for the development or exacerbation of autoimmune diseases such as systemic lupus erythematosus in the genetically predisposed individual. Molecular mimicry and engagement of TLRs have been assigned limited roles that link infection to autoimmunity, but additional mechanisms are suspected to be involved. In this study we show that T cells from
lupus
-prone mice display aggregated lipid rafts that harbor signaling, costimulatory, inflammatory, adhesion, and TLR molecules. The percentage of T cells with clustered lipid rafts increases with age and peaks before the development of
lupus
pathology. We show that
cholera
toxin B, a component of
Vibrio cholerae
, promotes autoantibody production and glomerulonephritis in
lupus
-prone mice by enhancing lipid raft aggregation in T cells. In contrast, disruption of lipid raft aggregation results in delay of disease pathology. Our results demonstrate that lipid rafts contribute significantly to the pathogenesis of
lupus
and provide a novel mechanism whereby aggregated lipid rafts represent a potential link between infection and autoimmunity.
...
PMID:Cholera toxin B accelerates disease progression in lupus-prone mice by promoting lipid raft aggregation. 1876 57
Some adjuvants may exert adverse effects upon injection or, on the other hand, may not trigger a full immunological reaction. The mechanisms underlying adjuvant adverse effects are under renewed scrutiny because of the enormous implications for vaccine development. In the search for new and safer adjuvants, several new adjuvants were developed by pharmaceutical companies utilizing new immunological and chemical innovations. The ability of the immune system to recognize molecules that are broadly shared by pathogens is, in part, due to the presence of special immune receptors called toll-like receptors (TLRs) that are expressed on leukocyte membranes. The very fact that TLR activation leads to adaptive immune responses to foreign entities explains why so many adjuvants used today in vaccinations are developed to mimic TLR ligands. Alongside their supportive role, adjuvants were found to inflict by themselves an illness of autoimmune nature, defined as 'the adjuvant diseases'. The debatable question of silicone as an adjuvant and connective tissue diseases, as well as the Gulf War syndrome and macrophagic myofaciitis which followed multiple injections of aluminium-based vaccines, are presented here. Owing to the adverse effects exerted by adjuvants, there is no doubt that safer adjuvants need to be developed and incorporated into future vaccines. Other needs in light of new vaccine technologies are adjuvants suitable for use with mucosally delivered vaccines, DNA vaccines, cancer and autoimmunity vaccines. In particular, there is demand for safe and non-toxic adjuvants able to stimulate cellular (Th1) immunity. More adjuvants were approved to date besides alum for human vaccines, including MF59 in some viral vaccines, MPL, AS04, AS01B and AS02A against viral and parasitic infections, virosomes for HBV, HPV and HAV, and
cholera
toxin for
cholera
. Perhaps future adjuvants occupying other putative receptors will be employed to bypass the TLR signaling pathway completely in order to circumvent common side effects of adjuvant-activated TLRs such as local inflammation and the general malaise felt because of the costly whole-body immune response to antigen.
Lupus
2009 Nov
PMID:Adjuvants and autoimmunity. 1988 May 72