α2AP is associated with the development of lupus nephritis through the regulation of plasmin inhibition and inflammatory responses.
Immun Inflamm Dis
; 8(3): 267-278, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32237065
ABSTRACT
INTRODUCTION:
Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE), which is a chronic autoimmune disease. However, the detailed mechanisms underlying this disorder have remained unclear. Alpha2-antiplasmin (α2AP) is known to perform various functions, such as plasmin inhibition and cytokine production, and to be associated with immune and inflammatory responses.METHODS:
We investigated the roles of α2AP in the pathogenesis of LN using a pristane-induced lupus mouse model.RESULTS:
The levels of plasmin-α2AP complex and α2AP were elevated in the lupus model mice. In addition, α2AP deficiency attenuated the pristane-induced glomerular cell proliferation, mesangial matrix expansion, collagen production, fibrin deposition, immunoglobulin G deposition, and proinflammatory cytokine production in the model mice. We also showed that interferon-γ (IFN-γ), which is an essential inducer of LN, induced α2AP production through the c-Jun N-terminal kinase (JNK) pathway in fibroblasts. In addition, plasmin attenuated the IFN-γ-induced proinflammatory cytokine production through the AMPK pathway in macrophages, and α2AP eliminated these effects. Furthermore, we showed that α2AP induced proinflammatory cytokine production through the ERK1/2 and JNK pathways in macrophages.CONCLUSION:
α2AP regulates the inflammatory responses through plasmin inhibition and proinflammatory cytokine production and is associated with the development of LN. Our findings may be used to develop a novel therapeutic approach for SLE.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nefrite Lúpica
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Immun Inflamm Dis
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Japão