| Texto completo | |
| Autor(es): |
Soares, Alexandre Learth
[1]
;
Coelho, Fernando Rodrigues
[1]
;
Guabiraba, Rodrigo
[2, 3]
;
Kamal, Mamdouh
[2, 3]
;
Boris Vargaftig, B.
[1]
;
Li, Lily
;
Li, Jian
[4]
;
Tavares-de-Lima, Wothan
[1]
;
Ryffel, Bernhard
[2, 3]
Número total de Autores: 9
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Dept Pharmacol, Inst Biomed Sci, Sao Paulo - Brazil
[2] Univ Orleans, Lab Mol Immunol & Embryol, F-45071 Orleans - France
[3] CNRS, UMR 6218, F-45071 Orleans - France
[4] Centocor R&D, Dept Immunobiol, Horsham, PA - USA
Número total de Afiliações: 4
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Shock; v. 34, n. 3, p. 306-313, SEP 2010. |
| Citações Web of Science: | 20 |
| Resumo | |
Intestinal ischemia-reperfusion (I/R) injury may cause acute systemic and lung inflammation. Here, we revisited the role of TNF-alpha in an intestinal I/R model in mice, showing that this cytokine is not required for the local and remote inflammatory response upon intestinal I/R injury using neutralizing TNF-alpha antibodies and TNF ligand-deficient mice. We demonstrate increased neutrophil recruitment in the lung as assessed by myeloperoxidase activity and augmented IL-6, granulocyte colony-stimulating factor, and KC levels, whereas TNF-alpha levels in serum were not increased and only minimally elevated in intestine and lung upon intestinal I/R injury. Importantly, TNF-alpha antibody neutralization neither diminished neutrophil recruitment nor any of the cytokines and chemokines evaluated. In addition, the inflammatory response was not abrogated in TNF and TNF receptors 1 and 2-deficient mice. However, in view of the damage on the intestinal barrier upon intestinal I/R with systemic bacterial translocation, we asked whether Toll-like receptor (TLR) activation is driving the inflammatory response. In fact, the inflammatory lung response is dramatically reduced in TLR2/4-deficient mice, confirming an important role of TLR receptor signaling causing the inflammatory lung response. In conclusion, endogenous TNF-alpha is not or minimally elevated and plays no role as a mediator for the inflammatory response upon ischemic tissue injury. By contrast, TLR2/4 signaling induces an orchestrated cytokine/chemokine response leading to local and remote pulmonary inflammation, and therefore disruption of TLR signaling may represent an alternative therapeutic target. (AU) | |
| Processo FAPESP: | 02/06606-3 - Fatores moduladores da inflamacao pulmonar experimental. |
| Beneficiário: | Wothan Tavares de Lima |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 03/02271-0 - Instilação intratraqueal de LPS ou suco gástrico como fator exacerbador da inflamação pulmonar ocasionada pelo trauma esplâncnico em camundongos |
| Beneficiário: | Alexandre Learth Soares |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| Processo FAPESP: | 04/14128-0 - Neuroimunomodulação: efeitos do estresse e de citocinas nas relações bidirecionais entre os sistemas nervosos central e imune |
| Beneficiário: | João Palermo Neto |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |