The pro-inflammatory cytokine TNF-α inhibits lymphatic pumping via activation of the NF-κB-iNOS signaling pathway.
Microcirculation
; 24(3)2017 04.
Article
en En
| MEDLINE
| ID: mdl-28231612
ABSTRACT
OBJECTIVE:
Mesenteric lymphatic vessel pumping, important to propel lymph and immune cells from the intestinal interstitium to the mesenteric lymph nodes, is compromised during intestinal inflammation. The objective of this study was to test the hypothesis that the pro-inflammatory cytokine TNF-α, is a significant contributor to the inflammation-induced lymphatic contractile dysfunction, and to determine its mode of action.METHODS:
Contractile parameters were obtained from isolated rat mesenteric lymphatic vessels mounted on a pressure myograph after 24-hours incubation with or without TNF-α. Various inhibitors were administered, and quantitative real-time PCR, Western blotting, and immunofluorescence confocal imaging were applied to characterize the mechanisms involved in TNF-α actions.RESULTS:
Vessel contraction frequency was significantly decreased after TNF-α treatment and could be restored by selective inhibition of NF-кB, iNOS, guanylate cyclase, and ATP-sensitive K+ channels. We further demonstrated that NF-кB inhibition also suppressed the significant increase in iNOS mRNA observed in TNF-α-treated lymphatic vessels and that TNF-α treatment favored the nuclear translocation of the p65 NF-κB subunit.CONCLUSIONS:
These findings suggest that TNF-α decreases mesenteric lymphatic contractility by activating the NF-κB-iNOS signaling pathway. This mechanism could contribute to the alteration of lymphatic pumping reported in intestinal inflammation.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
FN-kappa B
/
Factor de Necrosis Tumoral alfa
/
Vasos Linfáticos
/
Óxido Nítrico Sintasa de Tipo II
Límite:
Animals
Idioma:
En
Revista:
Microcirculation
Asunto de la revista:
ANGIOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Canadá