Impact of the innate immune response on mammary epithelia

Lipocalin 2 (Lcn2) is a member of the lipocalin family, members of which are usually small extracellular proteins with the abilities of binding and transporting small hydrophobic molecules. Lcn2 was named neutrophil gelatinase-associated lipocalin (NGAL) in human, neu related lipocalin (NRL) in rat and SIP24, 24p3, uterocalin, and siderocalin in mouse. The expression level of Lcn2 in the mammary gland is very high during involution. Results in this thesis show that the expression of rat Lcn2 (NRL) is higher in primiparous rat mammary glands after 28 days of involution than its expression in age matched virgin (AMV) mammary glands. Parity is associated with a lower incidence of breast cancer. The population size of macrophages in primiparous mammary glands is also higher in parous glands. More immune surveillance provided by the larger number of macrophages in the mammary gland after involution may be one reason for the observed parity induced protection against breast cancer. The expression levels of Lcn2 and other inflammatory genes are induced in HC11 cells, a mammary gland epithelial cell line, by mycoplasma infection or the mycoplasma membrane lipopeptide macrophage-activating lipopeptide-2 (MALP-2). Using the Lcn2 promoter linked to a luciferase reporter plasmid, we investigated the mechanism by which MALP-2 regulates gene expression and demonstrated that it activates NFkappaB and C/EBP and induces IkappaBzeta;. Reduction in IkappaBzeta by RNAi reduced Lcn2 promoter activation by MALP-2