期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 309, 期 3, 页码 G171-G180出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00126.2015
关键词
breast milk; necrotizing enterocolitis; TGF-beta(2); inflammation; chondroitinase
资金
- National Institutes of Health [R01 HD-059142, P01 HL-107152]
- Robert Wood Johnson Foundation [67067]
- UT Health Science Center at San Antonio-Clinical & Translational Science Award [UL1RR025767]
- American Diabetes Association [ID7-11-BS13]
- Gerber Foundation
Human milk contains biologically important amounts of transforming growth factor-beta(2) isoform (TGF-beta(2)), which is presumed to protect against inflammatory gut mucosal injury in the neonate. In preclinical models, enterally administered TGF-beta(2) can protect against experimental necrotizing enterocolitis, an inflammatory bowel necrosis of premature infants. In this study, we investigated whether TGF-beta bioactivity in human preterm milk could be enhanced for therapeutic purposes by adding recombinant TGF-beta(2) (rTGF-beta(2)) to milk prior to feeding. Milk-borne TGF-beta bioactivity was measured by established luciferase reporter assays. Molecular interactions of TGF-beta(2) were investigated by nondenaturing gel electrophoresis and immunoblots, computational molecular modeling, and affinity capillary electrophoresis. Addition of rTGF-beta(2) (20-40 nM) to human preterm milk samples failed to increase TGF-beta bioactivity in milk. Milk-borne TGF-beta(2) was bound to chondroitin sulfate (CS) containing proteoglycan(s) such as biglycan, which are expressed in high concentrations in milk. Chondroitinase treatment of milk increased the bioactivity of both endogenous and rTGF-beta(2), and consequently, enhanced the ability of preterm milk to suppress LPS-induced NF-kappa B activation in macrophages. These findings provide a mechanism for the normally low bioavailability of milk-borne TGF-beta(2) and identify chondroitinase digestion of milk as a potential therapeutic strategy to enhance the anti-inflammatory effects of preterm milk.
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