RESUMEN
BACKGROUND: Fibroblasts play a critical role in intestinal wound healing. Lipopolysaccharide (LPS) is a cell wall component of commensal gut bacteria. The effects of LPS on intestinal fibroblast activation were characterized. METHODS: Expression of the LPS receptor, toll-like receptor (TLR) 4, was assessed in cultured primary human intestinal fibroblasts using flow cytometry and confocal microscopy. Fibroblasts were treated with LPS and/or transforming growth factor (TGF) beta1. Nuclear factor kappaB (NFkappaB) pathway activation was assessed by inhibitory kappaBalpha (IkappaBalpha) degradation and NFkappaB promoter activity. Fibroblast contractility was measured using a fibroblast-populated collagen lattice. Smad-7, a negative regulator of TGF-beta1 signalling, and connective tissue growth factor (CTGF) expression were assessed using reverse transcriptase-polymerase chain reaction and western blot. The NFkappaB pathway was inhibited by IkappaBalpha transfection. RESULTS: TLR-4 was present on the surface of intestinal fibroblasts. LPS treatment of fibroblasts induced IkappaBalpha degradation, enhanced NFkappaB promoter activity and increased collagen contraction. Pretreatment with LPS (before TGF-beta1) significantly increased CTGF production relative to treatment with TGF-beta1 alone. LPS reduced whereas TGF-beta1 increased smad-7 expression. Transfection with an IkappaBalpha plasmid enhanced basal smad-7 expression. CONCLUSION: Intestinal fibroblasts express TLR-4 and respond to LPS by activating NFkappaB and inducing collagen contraction. LPS acts in concert with TGF-beta1 to induce CTGF. LPS reduces the expression of the TGF-beta1 inhibitor, smad-7.
Asunto(s)
Fibroblastos/efectos de los fármacos , Lipopolisacáridos/farmacología , Receptor Toll-Like 4/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Cicatrización de Heridas/fisiología , Anciano , Anciano de 80 o más Años , Células Cultivadas , Neoplasias del Colon/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/biosíntesis , Fibroblastos/metabolismo , Humanos , Quinasa I-kappa B/metabolismo , Persona de Mediana Edad , FN-kappa B/metabolismo , Proteína smad7/metabolismoRESUMEN
Music can touch patients deeply and thus transform their anxiety and stress into relaxation and healing. Patients with cancer who undergo surgical procedures are highly stressed. To help alleviate these patients' stress and improve their comfort, perioperative nurses at Memorial Sloan-Kettering Cancer Center (MSKCC), New York, surveyed surgical patients and staff members about introducing a perioperative music program. This article reviews the literature on the use of music in perioperative care settings and describes MSKCC's decision to evaluate and then implement a music program.