{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T10:38:20Z","timestamp":1761561500533},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T00:00:00Z","timestamp":1296518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. pediatr. gastroenterol. nutr."],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives:<\/jats:title><jats:p>CD40, a co\u2010stimulatory molecule, plays a critical role in coordinating enteric inflammatory immune responses. In necrotizing enterocolitis (NEC), upregulation of IL\u201010, a CD40\u2010modulated cytokine, has been described, but the role of the IL\u201010 receptor (IL\u201010R\u03b2), CD40, and its ligand CD40L in disease pathogenesis is unknown. The study herein investigates ileal expression of CD40, CD40L, and IL\u201010R in a rat model of NEC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and Methods:<\/jats:title><jats:p>NEC was induced in newborn rats using established methods of formula feeding, asphyxia, and cold stress. Expression of CD40, CD40L, IL\u201010R\u03b2, and other proinflammatory molecules, including Toll\u2010like receptor\u20104 (TLR\u20104) and IL\u201018, was assessed by immunoblotting. Tissue infiltration by macrophages, monocytes, and T cells was examined by confocal immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Ileum from rat pups with NEC showed increased expression of TLR\u20104, IL\u201018, and IL\u201010R\u03b2. Sections from both NEC and control pups demonstrated preservation of ileal cells expressing CD40\/CD40L. The distal ileum of controls expressed both CD40 and CD40L; conversely, neither molecule was detected in ileal tissue from NEC pups. Additional studies showed that treatment with epidermal growth factor (EGF), previously shown to ameliorate the severity of NEC in an animal model, did not restore CD40 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>Ileal cytokine dysregulation, manifested by decreased CD40\/CD40L and increased IL\u201010R\u03b2 expression, may be involved in the pathogenesis of NEC. Dampened CD40 signaling may be related to enhanced IL\u201010 expression and a suppressed T\u2010cell response to injury. We speculate that augmenting CD40\u2010CD40L interactions may achieve a protective effect in this NEC model.<\/jats:p><\/jats:sec>","DOI":"10.1097\/mpg.0b013e3182039bad","type":"journal-article","created":{"date-parts":[[2011,1,15]],"date-time":"2011-01-15T06:18:12Z","timestamp":1295072292000},"page":"140-146","source":"Crossref","is-referenced-by-count":13,"title":["Ileal Immune Dysregulation in Necrotizing Enterocolitis: Role of CD40\/CD40L in the Pathogenesis of Disease"],"prefix":"10.1002","volume":"52","author":[{"given":"Jiliu","family":"Xu","sequence":"first","affiliation":[{"name":"Division of Pediatric Gastroenterology USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R","family":"Treem","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Roman","sequence":"additional","affiliation":[{"name":"Cell Biology USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"Anderson","sequence":"additional","affiliation":[{"name":"Neurology and Physiology\/Pharmacology SUNY\u2010Downstate Medical Center USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Rubenstein","sequence":"additional","affiliation":[{"name":"Division of Pathology Kings County Hospital Center Brooklyn NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven M","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology 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