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Therapeutic ultrasound attenuates DSS-induced colitis through the cholinergic anti-inflammatory pathway.
Nunes, Natalia Schneider; Chandran, Parwathy; Sundby, Maggie; Visioli, Fernanda; da Costa Gonçalves, Fabiany; Burks, Scott Robert; Paz, Ana Helena; Frank, Joseph Alan.
Afiliación
  • Nunes NS; Frank Laboratory, Radiology and Imaging Sciences, Clinical Centre, NIH, Bethesda, MD, United States; Gastroenterology and Hepatology Sciences Graduate Program, UFRGS, Porto Alegre, RS, Brazil. Electronic address: natalia.schneidernunes@nih.gov.
  • Chandran P; Frank Laboratory, Radiology and Imaging Sciences, Clinical Centre, NIH, Bethesda, MD, United States.
  • Sundby M; Frank Laboratory, Radiology and Imaging Sciences, Clinical Centre, NIH, Bethesda, MD, United States.
  • Visioli F; Faculty of Dentistry, Oral Pathology, UFRGS, Porto Alegre, RS, Brazil.
  • da Costa Gonçalves F; Experimental Research Centre, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
  • Burks SR; Frank Laboratory, Radiology and Imaging Sciences, Clinical Centre, NIH, Bethesda, MD, United States.
  • Paz AH; Gastroenterology and Hepatology Sciences Graduate Program, UFRGS, Porto Alegre, RS, Brazil.
  • Frank JA; Frank Laboratory, Radiology and Imaging Sciences, Clinical Centre, NIH, Bethesda, MD, United States; National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, MD, United States.
EBioMedicine ; 45: 495-510, 2019 Jul.
Article en En | MEDLINE | ID: mdl-31253515
BACKGROUND: Ulcerative Colitis (UC) is an Inflammatory Bowel Disease (IBD) characterized by uncontrolled immune response, diarrhoea, weight loss and bloody stools, where sustained remission is not currently achievable. Dextran Sulphate Sodium (DSS)-induced colitis is an animal model that closely mimics human UC. Ultrasound (US) has been shown to prevent experimental acute kidney injury through vagus nerve (VN) stimulation and activation of the cholinergic anti-inflammatory pathway (CAIP). Since IBD patients may present dysfunctional VN activity, our aim was to determine the effects of therapeutic ultrasound (TUS) in DSS-induced colitis. METHODS: Acute colitis was induced by 2% DSS in drinking water for 7 days and TUS was administered to the abdominal area for 7 min/day from days 4-10. Clinical symptoms were analysed, and biological samples were collected for proteomics, macroscopic and microscopic analysis, flow cytometry and immunohistochemistry. FINDINGS: TUS attenuated colitis by reducing clinical scores, colon shortening and histological damage, inducing proteomic tolerogenic response in the gut during the injury phase and early recovery of experimental colitis. TUS did not improve clinical and pathological outcomes in splenectomised mice, while α7nAChR (α7 nicotinic acetylcholine receptor - indicator of CAIP involvement) knockout animals presented with disease worsening. Increased levels of colonic F4/80+α7nAChR+ macrophages in wild type mice suggest CAIP activation. INTERPRETATION: These results indicate TUS improved DSS-induced colitis through stimulation of the splenic nerve along with possible contribution by VN with CAIP activation. FUND: Intramural Research Programs of the Clinical Centre, the National Institute of Biomedical Imaging and Bioengineering at the NIH and CAPES/Brazil.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia por Ultrasonido / Enfermedades Inflamatorias del Intestino / Colitis / Inflamación Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: EBioMedicine Año: 2019 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia por Ultrasonido / Enfermedades Inflamatorias del Intestino / Colitis / Inflamación Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: EBioMedicine Año: 2019 Tipo del documento: Article Pais de publicación: Países Bajos