Fiona Yull

Last active: 3/21/2018

Activation of nuclear factor kappa B in mammary epithelium promotes milk loss during mammary development and infection.

Connelly L, Barham W, Pigg R, Saint-Jean L, Sherrill T, Cheng DS, Chodosh LA, Blackwell TS, Yull FE
J Cell Physiol. 2010 222 (1): 73-81

PMID: 19746431 · PMCID: PMC2783968 · DOI:10.1002/jcp.21922

We investigated whether nuclear factor kappa B (NF-kappaB), which exhibits a regulated pattern of activity during murine mammary gland development, plays an important role during lactation and involution, when milk production ceases and the gland undergoes apoptosis and re-modeling. We generated a doxycycline inducible transgenic mouse model to activate NF-kappaB specifically in the mammary epithelium through expression of a constitutively active form of IKK2, the upstream kinase in the classical NF-kappaB signaling cascade. We found that activation of NF-kappaB during involution resulted in a more rapid reduction in milk levels and increased cleavage of caspase-3, an indicator of apoptosis. We also found that activation of NF-kappaB during lactation with no additional involution signals had a similar effect. The observation that NF-kappaB is a key regulator of milk production led us to investigate the role of NF-kappaB during mastitis, an infection of the mammary gland in which milk loss is observed. Mammary gland injection of E. coli LPS resulted in activation of NF-kappaB and milk loss during lactation. This milk loss was decreased by selective inhibition of NF-kappaB in mammary epithelium. Together, our data reveal that activation of NF-kappaB leads to milk clearance in the lactating mammary gland. Therefore, targeting of NF-kappaB signaling may prove therapeutic during mastitis in humans and could be beneficial for the dairy industry, where such infections have a major economic impact.

MeSH Terms (18)

Animals Apoptosis Disease Models, Animal Doxycycline Epithelial Cells Epithelium Female Lactation Lipopolysaccharides Mammary Glands, Animal Mastitis Mice Mice, Transgenic Milk Milk Proteins NF-kappa B Signal Transduction Up-Regulation

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