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Analysis of Inflammatory Modulation on Term and Preterm Neonatal Gastrointestinal Non‐Human Primate Explants
Author(s) -
Alaicholas B,
Acevedo Steven J,
Carr Nick J,
Mustafa Shamimunisa B,
Blanco Cynthia L,
King Jonathan M
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1023.13
Subject(s) - ileum , medicine , epidermal growth factor , prostaglandin e2 , endocrinology , biology , receptor
BACKGROUND Dysregulation of inflammatory processes are associated with intestinal injury, necrotizing enterocolitis, and risk of perforation in the newborn. A reduction of Epidermal Growth Factor (EGF) and impaired function of the Epidermal Growth Factor Receptor (EGFR), have been demonstrated in the preterm gastrointestinal system compared to term. Prostaglandin E2 (PGE2) as well as EGF have independently been shown to have a role in the barrier maintenance, recovery from injury, and regulation of perfusion. OBJECTIVE Evaluate the regulation of EGF/EGFR/PGE2 pathway in a non‐human primate gastrointestinal explant. Additionally evaluating the roles of inflammatory and anti‐inflammatory agents on this pathway. DESIGN/METHODS Tissue explants were created from gastrointestinal regions (ileum through colon) upon necropsy of term and preterm (67% gestation) non‐human primates. Explants were evaluated in conditions of control, pro‐inflammatory (TNF 10 ng/ml), and anti‐inflammatory (indomethacin 50uM) variables. Absolute and relative prostaglandin secretion (PGE2); mRNA expression of Prostanoid (EP) receptor subtypes, EGFR, EPS8, AKT1, AKT2, and MAPK1 were used as markers of EGF/PGE2 pathway regulation at 24 hours post exposure. RESULTS PGE2 secretion significantly increases in term colon compared preterm colonic secretion. In addition, the term gastrointestinal explants are significantly more resistant to indomethacin inhibition of PGE2 secretion, noted across ileum, cecum, and colon. There were no significant differences noted in EP receptor subtype expression. Preterm expression of EGFR and its downstream effectors are elevated when compared to term ileum explants. However, there is markedly more variability in response noted to TNF and indomethacin in the term explants when compared to preterm ileum explants. CONCLUSIONS A positive gradient of PGE2 secretion in the distal gastrointestinal regions is observed in term explants likely correlated to the advanced differentiation status compared to the preterm. In addition, the up regulation of EGFR along with overall increased expression of downstream targets in the preterm explant is consistent with the expected mitogenic status. However, the decreased response to TNF and indomethacin, suggest a limited ability to modulate inflammation.