Preterm human milk contains a large pool of latent TGF-β, which can be activated by exogenous neuraminidase
Kopperuncholan Namachivayam, Cynthia L. Blanco, Brandy L. Frost, Aaron A. Reeves, Ramasamy Jagadeeswaran, Krishnan Mohankumar, Azif Safarulla, Partha Mandal, Steven A. Garzon, J. Usha Raj, Akhil Maheshwari
Human milk contains substantial amounts of transforming growth factor (TGF)-β, particularly the isoform TGF-β2. We previously showed in preclinical models that enterally administered TGF-β2 can protect against necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of premature infants. In this study we hypothesized that premature infants remain at higher risk of NEC than full-term infants, even when they receive their own mother's milk, because preterm human milk contains less bioactive TGF-β than full-term milk. Our objective was to compare TGF-β bioactivity in preterm vs. full-term milk and identify factors that activate milk-borne TGF-β Mothers who delivered between 23 0/7 and 31 6/7 wk or at ≥37 wk of gestation provided milk samples at serial time points. TGF-β bioactivity and NF-κB signaling were measured using specific reporter cells and in murine intestinal tissue explants. TGF-β1, TGF-β2, TGF-β3, and various TGF-β activators were measured by real-time PCR, enzyme immunoassays, or established enzymatic activity assays. Preterm human milk showed minimal TGF-β bioactivity in the native state but contained a large pool of latent TGF-β. TGF-β2 was the predominant isoform of TGF-β in preterm milk. Using a combination of several in vitro and ex vivo models, we show that neuraminidase is a key regulator of TGF-β bioactivity in human milk. Finally, we show that addition of bacterial neuraminidase to preterm human milk increased TGF-β bioactivity. Preterm milk contains large quantities of TGF-β, but most of it is in an inactive state. Addition of neuraminidase can increase TGF-β bioactivity in preterm milk and enhance its anti-inflammatory effects.
G1055-G1065
American Journal of Physiology - Gastrointestinal and Liver Physiology
https://doi.org/10.1152/ajpgi.00039.2013
Necrotizing enterocolitis
Sialidase
Transforming growth factor-β
10.1152/ajpgi.00039.2013
Dive into the research topics of 'Preterm human milk contains a large pool of latent TGF-β, which can be activated by exogenous neuraminidase'. Together they form a unique fingerprint.
Transforming Growth Factor Pharmacology, Toxicology and Pharmaceutical Science 100%
Milk Food Science 17%
Human Milk Medicine and Dentistry 8%
Biological Activity Medicine and Dentistry 7%
Prothrombin Pharmacology, Toxicology and Pharmaceutical Science 5%
Sialidase Pharmacology, Toxicology and Pharmaceutical Science 5%
Neuraminidase Biochemistry, Genetics and Molecular Biology 3%
Prematurity Pharmacology, Toxicology and Pharmaceutical Science 2%
Namachivayam, K., Blanco, C. L., Frost, B. L., Reeves, A. A., Jagadeeswaran, R., Mohankumar, K., Safarulla, A., Mandal, P., Garzon, S. A., Raj, J. U., & Maheshwari, A. (2013). Preterm human milk contains a large pool of latent TGF-β, which can be activated by exogenous neuraminidase. American Journal of Physiology - Gastrointestinal and Liver Physiology, 304(12), G1055-G1065. https://doi.org/10.1152/ajpgi.00039.2013
Preterm human milk contains a large pool of latent TGF-β, which can be activated by exogenous neuraminidase. / Namachivayam, Kopperuncholan; Blanco, Cynthia L.; Frost, Brandy L. et al.
In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 304, No. 12, 16.06.2013, p. G1055-G1065.
Namachivayam, K, Blanco, CL, Frost, BL, Reeves, AA, Jagadeeswaran, R, Mohankumar, K, Safarulla, A, Mandal, P, Garzon, SA, Raj, JU & Maheshwari, A 2013, 'Preterm human milk contains a large pool of latent TGF-β, which can be activated by exogenous neuraminidase', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 304, no. 12, pp. G1055-G1065. https://doi.org/10.1152/ajpgi.00039.2013
Namachivayam K, Blanco CL, Frost BL, Reeves AA, Jagadeeswaran R, Mohankumar K et al. Preterm human milk contains a large pool of latent TGF-β, which can be activated by exogenous neuraminidase. American Journal of Physiology - Gastrointestinal and Liver Physiology. 2013 Jun 16;304(12):G1055-G1065. doi: 10.1152/ajpgi.00039.2013
Namachivayam, Kopperuncholan ; Blanco, Cynthia L. ; Frost, Brandy L. et al. / Preterm human milk contains a large pool of latent TGF-β, which can be activated by exogenous neuraminidase. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2013 ; Vol. 304, No. 12. pp. G1055-G1065.
@article{5f3d4099e8e142dcbb762b8cce6c1260,
title = "Preterm human milk contains a large pool of latent TGF-β, which can be activated by exogenous neuraminidase",
abstract = "Human milk contains substantial amounts of transforming growth factor (TGF)-β, particularly the isoform TGF-β2. We previously showed in preclinical models that enterally administered TGF-β2 can protect against necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of premature infants. In this study we hypothesized that premature infants remain at higher risk of NEC than full-term infants, even when they receive their own mother's milk, because preterm human milk contains less bioactive TGF-β than full-term milk. Our objective was to compare TGF-β bioactivity in preterm vs. full-term milk and identify factors that activate milk-borne TGF-β Mothers who delivered between 23 0/7 and 31 6/7 wk or at ≥37 wk of gestation provided milk samples at serial time points. TGF-β bioactivity and NF-κB signaling were measured using specific reporter cells and in murine intestinal tissue explants. TGF-β1, TGF-β2, TGF-β3, and various TGF-β activators were measured by real-time PCR, enzyme immunoassays, or established enzymatic activity assays. Preterm human milk showed minimal TGF-β bioactivity in the native state but contained a large pool of latent TGF-β. TGF-β2 was the predominant isoform of TGF-β in preterm milk. Using a combination of several in vitro and ex vivo models, we show that neuraminidase is a key regulator of TGF-β bioactivity in human milk. Finally, we show that addition of bacterial neuraminidase to preterm human milk increased TGF-β bioactivity. Preterm milk contains large quantities of TGF-β, but most of it is in an inactive state. Addition of neuraminidase can increase TGF-β bioactivity in preterm milk and enhance its anti-inflammatory effects.",
keywords = "Breast milk, Inflammation, Necrotizing enterocolitis, Sialidase, Transforming growth factor-β",
author = "Kopperuncholan Namachivayam and Blanco, {Cynthia L.} and Frost, {Brandy L.} and Reeves, {Aaron A.} and Ramasamy Jagadeeswaran and Krishnan Mohankumar and Azif Safarulla and Partha Mandal and Garzon, {Steven A.} and Raj, {J. Usha} and Akhil Maheshwari",
doi = "10.1152/ajpgi.00039.2013",
pages = "G1055--G1065",
journal = "American Journal of Physiology - Renal Physiology",
publisher = "American Physiological Society",
T1 - Preterm human milk contains a large pool of latent TGF-β, which can be activated by exogenous neuraminidase
AU - Namachivayam, Kopperuncholan
AU - Blanco, Cynthia L.
AU - Frost, Brandy L.
AU - Reeves, Aaron A.
AU - Jagadeeswaran, Ramasamy
AU - Mohankumar, Krishnan
AU - Safarulla, Azif
AU - Mandal, Partha
AU - Garzon, Steven A.
AU - Raj, J. Usha
AU - Maheshwari, Akhil
N2 - Human milk contains substantial amounts of transforming growth factor (TGF)-β, particularly the isoform TGF-β2. We previously showed in preclinical models that enterally administered TGF-β2 can protect against necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of premature infants. In this study we hypothesized that premature infants remain at higher risk of NEC than full-term infants, even when they receive their own mother's milk, because preterm human milk contains less bioactive TGF-β than full-term milk. Our objective was to compare TGF-β bioactivity in preterm vs. full-term milk and identify factors that activate milk-borne TGF-β Mothers who delivered between 23 0/7 and 31 6/7 wk or at ≥37 wk of gestation provided milk samples at serial time points. TGF-β bioactivity and NF-κB signaling were measured using specific reporter cells and in murine intestinal tissue explants. TGF-β1, TGF-β2, TGF-β3, and various TGF-β activators were measured by real-time PCR, enzyme immunoassays, or established enzymatic activity assays. Preterm human milk showed minimal TGF-β bioactivity in the native state but contained a large pool of latent TGF-β. TGF-β2 was the predominant isoform of TGF-β in preterm milk. Using a combination of several in vitro and ex vivo models, we show that neuraminidase is a key regulator of TGF-β bioactivity in human milk. Finally, we show that addition of bacterial neuraminidase to preterm human milk increased TGF-β bioactivity. Preterm milk contains large quantities of TGF-β, but most of it is in an inactive state. Addition of neuraminidase can increase TGF-β bioactivity in preterm milk and enhance its anti-inflammatory effects.
AB - Human milk contains substantial amounts of transforming growth factor (TGF)-β, particularly the isoform TGF-β2. We previously showed in preclinical models that enterally administered TGF-β2 can protect against necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of premature infants. In this study we hypothesized that premature infants remain at higher risk of NEC than full-term infants, even when they receive their own mother's milk, because preterm human milk contains less bioactive TGF-β than full-term milk. Our objective was to compare TGF-β bioactivity in preterm vs. full-term milk and identify factors that activate milk-borne TGF-β Mothers who delivered between 23 0/7 and 31 6/7 wk or at ≥37 wk of gestation provided milk samples at serial time points. TGF-β bioactivity and NF-κB signaling were measured using specific reporter cells and in murine intestinal tissue explants. TGF-β1, TGF-β2, TGF-β3, and various TGF-β activators were measured by real-time PCR, enzyme immunoassays, or established enzymatic activity assays. Preterm human milk showed minimal TGF-β bioactivity in the native state but contained a large pool of latent TGF-β. TGF-β2 was the predominant isoform of TGF-β in preterm milk. Using a combination of several in vitro and ex vivo models, we show that neuraminidase is a key regulator of TGF-β bioactivity in human milk. Finally, we show that addition of bacterial neuraminidase to preterm human milk increased TGF-β bioactivity. Preterm milk contains large quantities of TGF-β, but most of it is in an inactive state. Addition of neuraminidase can increase TGF-β bioactivity in preterm milk and enhance its anti-inflammatory effects.
KW - Breast milk
KW - Necrotizing enterocolitis
KW - Sialidase
KW - Transforming growth factor-β
U2 - 10.1152/ajpgi.00039.2013
DO - 10.1152/ajpgi.00039.2013
SP - G1055-G1065
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology