BACKGROUND: Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disease in premature infants with high mortality and morbidity with uncertain pathogenesis. Recent research focused on the role of intraluminal bacteria and lipopolysaccharide (LPS). However, an additional role of viral agents in the pathogenesis of NEC has recently been postulated. We assessed the role of polyinosinic:polycytidylic acid (pIC) mimicking viral dsRNA in contributing to the development of NEC in neonatal mice. METHODS: Four-d-old C57BL/6J pups were stressed by asphyxia and hypothermia twice daily. Animals were either fed by formula only (FO), formula containing LPS or pIC. After 72 h, mice were euthanized, intestines harvested, and the severity of NEC was assessed. RESULTS: Breastfed mice showed no evidence of NEC. Very mild NEC-like lesions were observed in mice fed by FO. Supplementation of LPS or pIC to the formula led to increased intestinal tissue damage and inflammation compared with FO in a similar manner. CONCLUSION: Our study demonstrates the ability of viral factors to induce NEC in neonatal mice even in the absence of LPS. Furthermore, we present a new mouse model of pIC-induced NEC which may be used to obtain further mechanistic insights in the pathogenesis of this disease.
BACKGROUND:Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disease in premature infants with high mortality and morbidity with uncertain pathogenesis. Recent research focused on the role of intraluminal bacteria and lipopolysaccharide (LPS). However, an additional role of viral agents in the pathogenesis of NEC has recently been postulated. We assessed the role of polyinosinic:polycytidylic acid (pIC) mimicking viral dsRNA in contributing to the development of NEC in neonatal mice. METHODS: Four-d-old C57BL/6J pups were stressed by asphyxia and hypothermia twice daily. Animals were either fed by formula only (FO), formula containing LPS or pIC. After 72 h, mice were euthanized, intestines harvested, and the severity of NEC was assessed. RESULTS: Breastfed mice showed no evidence of NEC. Very mild NEC-like lesions were observed in mice fed by FO. Supplementation of LPS or pIC to the formula led to increased intestinal tissue damage and inflammation compared with FO in a similar manner. CONCLUSION: Our study demonstrates the ability of viral factors to induce NEC in neonatal mice even in the absence of LPS. Furthermore, we present a new mouse model of pIC-induced NEC which may be used to obtain further mechanistic insights in the pathogenesis of this disease.
Authors: Chhinder P Sodhi; Xia-Hua Shi; Ward M Richardson; Zachary S Grant; Richard A Shapiro; Thomas Prindle; Maria Branca; Anthony Russo; Steven C Gribar; Congrong Ma; David J Hackam Journal: Gastroenterology Date: 2009-09-26 Impact factor: 22.682
Authors: Cynthia L Leaphart; Jaime Cavallo; Steven C Gribar; Selma Cetin; Jun Li; Maria F Branca; Theresa D Dubowski; Chhinder P Sodhi; David J Hackam Journal: J Immunol Date: 2007-10-01 Impact factor: 5.422
Authors: Renu Sharma; Robert D Garrison; J J Tepas; Daniel L Mollitt; Pam Pieper; Mark L Hudak; James A Bradshaw; Gary Stevens; Bangalore R Premachandra Journal: J Pediatr Surg Date: 2004-03 Impact factor: 2.545
Authors: Selma Cetin; Henri R Ford; Laura R Sysko; Charu Agarwal; James Wang; Matthew D Neal; Catherine Baty; Gerard Apodaca; David J Hackam Journal: J Biol Chem Date: 2004-03-30 Impact factor: 5.157
Authors: Reina M Turcios-Ruiz; Peter Axelrod; Keith St John; Esther Bullitt; Joan Donahue; Nancy Robinson; Helena E Friss Journal: J Pediatr Date: 2008-06-05 Impact factor: 4.406
Authors: Marco Ginzel; Xiaoyan Feng; Joachim F Kuebler; Christian Klemann; Yi Yu; Reinhard von Wasielewski; Joon-Keun Park; Mathias W Hornef; Gertrud Vieten; Benno M Ure; Torsten Kaussen; Jan Hendrik Gosemann; Steffi Mayer; Anne Suttkus; Martin Lacher Journal: PLoS One Date: 2017-08-17 Impact factor: 3.240
Authors: I Martynov; W Göpel; T K Rausch; C Härtel; A Franke; A R Franz; D Viemann; U H Thome; M Lacher; B W Ackermann Journal: Sci Rep Date: 2021-07-02 Impact factor: 4.379