Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Signaling pathway and gene network regulation of NFkB and cytokine mRNA expression in Mastitis
Nicoline Y den Breems, Don Kulasiri

Last modified: 2014-03-27

Abstract


Mastitis is the result of an inflammation in the mammary gland. In humans, mastitis occurs in 18% of breastfeeding mothers and is associated with increased transmission of bacterial infections and Human Immunodeficiency Virus (HIV). In the Dairy industry, mastitis is a major cause of disease worldwide. In the USA, mastitis has been estimated to cost the industry US$1.7 billion annually. Despite extensive research, 30% of the cows are still affected by mastitis.

Differentially regulated cytokines have been identified, however the underlying mechanics of the NFkB signaling initiating the cytokine mRNA expression in mastitis are incompletely understood.

Isolates of mammary epithelial cells were cultured and challenged with E. coli bacteria for 1, 3, and 6 hours and mRNA applied to bovine Affymetrix microarrays. mRNA of the cytokines TNFa, IL8 and RANTES were identified as differentially regulated in the infection.

We developed a combined signalling and gene network regulation model with ordinary differential equations to represent the signalling pathway and cytokine mRNA expression levels. The developed model fit the experimental data well and sensitivity analysis identified the signalling and gene network regulation differences between the cytokines.


Keywords


GNR; ODE; mastitis