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Substance P in polymicrobial sepsis: molecular fingerprint of lung injury in preprotachykinin-A-/- mice.
Hegde, Akhil; Tamizhselvi, Ramasamy; Manikandan, Jayapal; Melendez, Alirio J; Moochhala, Shabbir M; Bhatia, Madhav.
Afiliación
  • Hegde A; Cardiovascular Biology Program, Department of Pharmacology, Yong Loo Lin School of Medicine,National University of Singapore, Singapore.
Mol Med ; 16(5-6): 188-98, 2010.
Article en En | MEDLINE | ID: mdl-20454520
Deletion of mouse preprotachykinin-A (PPTA), which encodes mainly for neuropeptide substance P, has been shown to protect against lung injury and mortality in sepsis. This study explored microarray-based differential gene expression profiles in mouse lung tissue 8 h after inducing microbial sepsis and the effect of PPTA gene deletion. A range of genes differentially expressed (more than two-fold) in microarray analysis was assessed, comparing wild-type and PPTA-knockout septic mice with their respective sham controls, and the data were further validated. Genetic deletion of substance P resulted in a significantly different expression profile of genes involved in inflammation and immunomodulation after the induction of sepsis, compared with wild-type mice. Interestingly, apart from the various proinflammatory mediators, the antiinflammatory cytokine interleukin-1 receptor antagonist gene (IL1RN) was also elevated much more in PPTA(-/-) septic mice. In addition, semiquantitative RT-PCR analysis supported the microarray data. The microarray data imply that the elevated levels of inflammatory gene expression in the early stages of sepsis in PPTA-knockout mice are possibly aimed to resolve the infection without excessive immunosuppression. As scientists are divided over the effects of pro- and antiinflammatory mediators in sepsis, it seems prudent to define the status depending on a complete genome profile. This is the first report exploring pulmonary gene expression profiles using microarray analysis in PPTA-knockout mice subjected to cecal ligation and puncture-induced sepsis and providing additional biological insight into the protection received against lung injury and mortality.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Precursores de Proteínas / Taquicininas / Bacteriemia / Enfermedades Pulmonares Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2010 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Precursores de Proteínas / Taquicininas / Bacteriemia / Enfermedades Pulmonares Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2010 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Reino Unido