Role of adrenomedullin in Lyme disease.
Infect Immun
; 78(12): 5307-13, 2010 Dec.
Article
en En
| MEDLINE
| ID: mdl-20921145
ABSTRACT
Borrelia burgdorferi stimulates a strong inflammatory response during infection of a mammalian host. To understand the mechanisms of immune regulation employed by the host to control this inflammatory response, we focused our studies on adrenomedullin, a peptide produced in response to bacterial stimuli that exhibits antimicrobial activity and regulates inflammatory responses by modulating the expression of inflammatory cytokines. Specifically, we investigated the effect of B. burgdorferi on the expression of adrenomedullin as well as the ability of adrenomedullin to dampen host inflammatory responses to the spirochete. The concentration of adrenomedullin in the synovial fluid of untreated Lyme arthritis patients was elevated compared with that in control osteoarthritis patient samples. In addition, coculture with B. burgdorferi significantly increased the expression of adrenomedullin in RAW264.7 macrophages through MyD88-, phosphatidylinositol 3-kinase (PI3-K)-, and p38-dependent signaling cascades. Furthermore, the addition of exogenous adrenomedullin to B. burgdorferi-stimulated RAW264.7 macrophages resulted in a significant decrease in the induction of proinflammatory cytokines. Taken together, these results suggest that B. burgdorferi increases the production of adrenomedullin, which in turn negatively regulates the B. burgdorferi-stimulated inflammatory response.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Lyme
/
Adrenomedulina
Tipo de estudio:
Observational_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Infect Immun
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos