Interferon-γ Inhibits Intestinal Restitution by Preventing Gap Junction Communication Between Enterocytes

Leaphart, Cynthia L.; Qureshi, Faisal; Çetin, Selma; Li, Jun; Dubowski, Theresa; Batey, Catherine; Beer‐Stolz, Donna; Guo, Fei; Murray, Sandra A.; Hackam, David J.

doi:10.1053/j.gastro.2007.03.029

Cited by 91 publications

(98 citation statements)

References 62 publications

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“…Our observations made in splenocytes of untreated rats show that CB-01-05 interferes with cytokines profile, reducing the production of IFN-c and increasing the expression of TNF-a, IL-2, and IL-10. The combined reduction of IFN-c and the increase of IL-10 could account for the observed anti-inflammatory activity of CB-01-05, considering the pivotal role of IFN-c in impairing intestinal healing [23], and the well-known immunoregulatory function of IL-10 [24]. CB-01-05 also shows a profile of activity different from that of UFH, resulting more effective as an inhibitor of IFN-c production, but consistently less potent in eliciting the release of TNF-a and, in particular, IL-2.…”

Section: Discussionmentioning

confidence: 97%

Efficacy of Intracolonic Administration of Low-Molecular-Weight Heparin CB-01-05, Compared to Other Low-Molecular-Weight Heparins and Unfractionated Heparin, in Experimentally Induced Colitis in Rat

et al. 2008

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Purpose Parenteral administration of lowmolecular-weight heparins (LMWHs) and unfractionated heparin (UFH) resulted effective in improving the symptoms of experimental colitis in rat. Today, there is little information about their activity by intracolonic instillation. The scope of this study was to evaluate the ability of CB-01-05 (a LMWH with a mean molecular weight of about 5,700), compared to a series of other LMWHs and to UFH, directly instilled into the distal colon of the rat, to ameliorate dinitrobenzene (DNB)-induced experimental colitis. Method Adult male Wistar rats underwent colitis induction by intracolonic instillation of DNB. Starting 24 h after colitis induction, CB-01-05 (0.005-0.9 mg), other LMWHs (0.3-0.6 mg), and UFH (0.6 mg) were instilled, by rectal route, into the distal colon once a day for three consecutive days. On the day following the last administration, the animals were sacrificed and the distal colon was isolated, weighed, macroscopically examined, and processed for histology. Additional experiments in rat splenocytes, performed in order to elucidate the anti-inflammatory mechanisms of CB-01-05, were performed. Results Among the tested items, only CB-01-05 at doses ranging from 0.2 to 0.9 mg was significantly effective in reducing colon weight increase and in improving both the mucosal damaged area and the histological score. The other LMWHs resulted far less effective, showing decreasing activity closely related with the decrease of their molecular weight, thus demonstrating their biological nonequivalence. CB-01-05 resulted also more active than UFH. CB-01-05 was shown to interfere with cytokines production by rat splenocytes, mainly inhibiting interferon (IFN)-c expression. Conclusions CB-01-05 instilled into the colon is well tolerated, has strong anti-inflammatory effect on DNBinduced colitis in rat, and is the most effective agent among other LMWHs and UFH. These results suggest that the anti-inflammatory activity of CB-01-05, together with its topical administration, could represent a new approach in the management of ulcerative colitis.

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Section: Discussionmentioning

confidence: 97%

Efficacy of Intracolonic Administration of Low-Molecular-Weight Heparin CB-01-05, Compared to Other Low-Molecular-Weight Heparins and Unfractionated Heparin, in Experimentally Induced Colitis in Rat

et al. 2008

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“…With this protocol, breastfeeding is almost avoided, which has been shown to be protective against NEC in both humans and rodents. However, it has also been reported that this effect does not reach 100% (13,16,35). Articles Ginzel et al…”

Section: Articlesmentioning

confidence: 98%

“…To account for the increase in body weight, the feeding volume was increased daily as tolerated (50, 60, and 70 μl on days 1, 2, and 3, respectively). Mice underwent stress exposure by asphyxia (100% nitrogen for 60 s, followed by exposure to cold (4 °C) for 10 min) twice daily prior to feeding as previously described (12,13,16,35).…”

Section: Neonatal Nec Mouse Modelmentioning

confidence: 99%

The viral dsRNA analogue poly (I:C) induces necrotizing enterocolitis in neonatal mice

Ginzel

Klemann

et al. 2015

Pediatr Res

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Background: Necrotizing enterocolitis (NEC) is a lifethreatening 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.

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“…Terminal ilea were flushed with saline to remove luminal contents, opened longitudinally and mucosal scrapings collected. NEC was induced in 2-3 week old C57Bl/6 mice by a combination of gavage formula (2:1 Similac Advanced infant formula (Ross Pediatrics):Esbilac canine milk replacer (Pet-Ag)) feeding 5 times per day (40µl/g) and exposure to intermittent hypoxia (100% N 2 ) for 90 seconds in a Billups-Rothenberg (Del-Mar, CA) hypoxia chamber twice daily for 4 days as previously described (19,20). Animals were sacrificed and serum and terminal ileal mucosal scrapings collected described above.…”

Section: In Vivo Induction Of Endotoxemia and Necrotizing Enterocolitismentioning

confidence: 99%

Increased expression and internalization of the endotoxin coreceptor CD14 in enterocytes occur as an early event in the development of experimental necrotizing enterocolitis

Mollen

Gribar

Anand

et al. 2008

Journal of Pediatric Surgery

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Background-The early signaling events in the development of necrotizing enterocolitis (NEC) remain undefined. We have recently shown that the endotoxin (lipopolysaccharide, LPS) receptor Toll-like receptor 4 (TLR4) on enterocytes is critical in the pathogenesis of experimental NEC. Given that the membrane receptor CD14 is known to facilitate the activation of TLR4, we now hypothesize that endotoxemia induces an early up-regulation of CD14 in enterocytes, and that this participates in the early intestinal inflammatory response in the development of NEC.

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Interferon-γ Inhibits Intestinal Restitution by Preventing Gap Junction Communication Between Enterocytes

Cited by 91 publications

References 62 publications

Efficacy of Intracolonic Administration of Low-Molecular-Weight Heparin CB-01-05, Compared to Other Low-Molecular-Weight Heparins and Unfractionated Heparin, in Experimentally Induced Colitis in Rat

Efficacy of Intracolonic Administration of Low-Molecular-Weight Heparin CB-01-05, Compared to Other Low-Molecular-Weight Heparins and Unfractionated Heparin, in Experimentally Induced Colitis in Rat

The viral dsRNA analogue poly (I:C) induces necrotizing enterocolitis in neonatal mice

Increased expression and internalization of the endotoxin coreceptor CD14 in enterocytes occur as an early event in the development of experimental necrotizing enterocolitis

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