Basic—Alimentary TractTGF-β2 Suppresses Macrophage Cytokine Production and Mucosal Inflammatory Responses in the Developing Intestine
Section snippets
Human Intestinal Tissue Samples
Human intestinal tissues were collected after approval by local Institutional Review Boards. Fetal intestinal tissue (11−24 weeks, n = 25) was obtained at elective terminations of pregnancy. Tissue samples of advanced NEC (n = 8) were compared with healthy tissue margins obtained during resection for indications other than NEC (premature neonates: repair of ostomy, n = 5; gestational age 27, 27.5, 28.5, 30.5, and 32 weeks; full-term neonates: atresia/obstruction; n = 3). Adult tissues were
Macrophages in the Preterm Human Intestine Express Inflammatory Cytokines
To investigate our hypothesis that the inflammatory down-regulation of intestinal macrophages is a function of gestational maturation, we first compared macrophages in intestinal tissue samples from human fetuses, premature and full-term neonates, and adults by immunohistochemistry for inflammatory cytokines. Consistent with existing information,6, 25 macrophages in the full-term neonatal and adult intestine did not express TNF-α or IL-8/CXCL8. However, macrophages in preterm intestine (from
Discussion
We present a detailed investigation into the normal development of LPS tolerance in intestinal macrophages and a novel pathophysiological model for NEC with possible therapeutic implications. In contrast to the noninflammatory functional profile of intestinal macrophages seen in the mature host, macrophages in the preterm intestine can respond to bacterial products to produce a robust inflammatory response. In the normal fetus, intestinal macrophages undergo progressive inflammatory
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by the National Institutes of Health awards HD059142, HD043397, American Gastroenterological Association 2006 Research Scholar Award, and a research grant from the CACA Jones Family Foundation (A.M.), National Institutes of Health grants HD046513, HL092906, ATS PH-06-006 (N.A.), and ES015323 (M.A.). Blood monocytes and adult jejunal tissue were received from Core 2 of the UAB Mucosal Immunology and HIV Center (DK64400). The work was made possible in part by the Research Facilities Improvement Grant C06RR15490 from the National Center for Research Resources.