Recent advances and opportunities in research on lupus: environmental influences and mechanisms of disease

Ciência & Saúde Coletiva

Glinda Cooper²  Kathleen Gilbert¹  Eric Greidinger¹  Judith James¹  Jean Pfau¹  Leslie Reinlib¹  Bruce Richardson¹  Noel Rose¹ 

[1],National Center for Environmental Assessment U.S. Environmental Protection Agency Washington DC ,USA

关键词: Apoptosis;    Epstein-Barr virus;    Silica;    Systemic lupus erythematosus;    Trichloroethylene;    Apoptose;    Vírus Epstein-Barr;    Sílica;    Lúpus eritematoso sistêmico;    Tricloroetileno;   

DOI  :  10.1590/S1413-81232009000500028

来源: SciELO

【 摘 要 】

We summarize research on mechanisms through which environmental agents may affect the pathogenesis of lupus, discuss three exposures that have been the focus of research in this area, and propose recommendations for new research initiatives. We examined studies pertaining to key mechanistic events and specific exposures. Apoptosis leading to increased production or decreased clearance of immunogenic intracellular self-antigens and defective apoptosis of autoreactive immune cells both have been implicated in the loss of self-tolerance. The adjuvant or bystander effect is also needed to produce a sustained autoimmune response. Activation of toll-like receptors is one mechanism through which these effects may occur. Abnormal DNA methylation may contribute to the pathogenesis of lupus. Each of the specific exposures has been shown, in humans or in mice, to act upon one or more of these pathogenic steps. Specific recommendations for the continued advancement of our understanding of environmental influences on lupus and other autoimmune diseases include the development and use of mouse models with varying degrees of penetrance and manifestations of disease, identification of molecular or physiologic targets of specific exposures, development and use of improved exposure assessment methodologies, and multisite collaborations designed to examine understudied environmental exposures in humans.

【 授权许可】

CC BY   
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