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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume304
Issue number12
DOIs
StatePublished - Jun 16 2013
Externally publishedYes

Fingerprint

Neuraminidase
Transforming Growth Factors
Human Milk
Milk
Necrotizing Enterocolitis
Premature Infants
Protein Isoforms
Mothers
Enzyme Assays

Keywords

  • Breast milk
  • Inflammation
  • Necrotizing enterocolitis
  • Sialidase
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

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.; Reeves, Aaron A.; Jagadeeswaran, Ramasamy; Mohankumar, Krishnan; Safarulla, Azif; Mandal, Partha; Garzon, Steven A.; Raj, J. Usha; Maheshwari, Akhil.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 304, No. 12, 16.06.2013.

Research output: Contribution to journalArticle

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. https://doi.org/10.1152/ajpgi.00039.2013
Namachivayam, Kopperuncholan ; Blanco, Cynthia L. ; Frost, Brandy L. ; Reeves, Aaron A. ; Jagadeeswaran, Ramasamy ; Mohankumar, Krishnan ; Safarulla, Azif ; Mandal, Partha ; Garzon, Steven A. ; Raj, J. Usha ; Maheshwari, Akhil. / 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.
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