Loss of IL-10 Decreases Mouse Postpubertal Mammary Gland Development in the Absence of Inflammation

Abstract

IL-10 is a pleiotrophic anti-inflammatory cytokine. Decreased IL-10 expression is associated with an increased breast cancer risk but the mechanism is not clear. This study was designed to test the hypothesis that the loss of IL-10 alters mammary development, even in the absence of inflammation. Wild-type and IL-10-/- mouse littermates were similar in growth, development, and breeding success. Using whole-mounts and paraffin sections, mammary glands from pre-pubertal mice (d21) were found to not be affected by the IL-10 null genotype. However, after the onset of estrous cycling, ductal structure, but not lymph nodes or adipocytes, of IL-10 knockout mice were found to moderately decrease at day 55, 80, and 150 of age. This phenotype was not rescued by lactogenesis. At day 2 of lactation, IL-10 null mice had reduced lobular complexity and glandular area with the retention of adipocytes. These results support the hypothesis that absence of IL-10 reduces glandular development during postnatal development, at maturity, and during the early stages of lactation. Although our study cannot distinguish between a direct IL-10 effect on the epithelial cells and an indirect systemic effect, epithelial cell responses to IL-10 should be considered in the therapeutic applications of cytokines or cytokine ablation.

The Effect of Dietary Prebiotics and Probiotics on Body Weight, Large Intestine Indices, and Fecal Bile Acid Profile in Wild Type and IL10−/− Mice

“…There was only one other animal study that has examined the effect of IL10 knockout in the absence of inflammation. In that study of female IL10−/− mice, less post-pubertal mammary glandular epithelial development was reported in the absence of inflammation [34].…”

“…Specific pathogen-free (SPF) [33] wild type C57BL/6 male mice were purchased from Taconic Farms, Inc. (Germantown, New York). The male IL10+/+ (wild type) and IL10−/− mice were generated by heterozygous inbreeding from our IL10-null colony [34]. Whenever possible, littermates were assigned to different dietary groups.…”

Dietary or supplemental fermentable fiber intake reduces the presence of Clostridium XI in mouse intestinal microbiota: The importance of higher fecal bacterial load and density

“…To ensure the effectiveness of our multiple steps in separating mouse DNA from the bacterial DNA, we performed PCR analysis of mouse genes in the extracted fecal DNA to validate the low mouse DNA contamination. Published PCR primers for three mouse genes, insulin-like growth factor 2, IL10 and sodium-dependent vitamin C transporter 2, were used and mouse tissue DNA that we have reported was used as the mouse DNA standard [ 24 , 25 ]. For the purpose of quality control in the microbiota analysis and in qPCR quantification, DNA was also extracted from a mixture of known concentrations of bacteria including Bifidobacterium lactis , B .…”

Gender Difference in Bacteria Endotoxin-Induced Inflammatory and Anorexic Responses

“…Protocols for mouse colony maintenance and mouse handling were approved by the Institutional Animal Care and Use Committee of the University at Buffalo. Male and female wildtype, IL10+/-, and IL10-/- mice were from an IL10+/- colony maintained in the UB specific pathogen-free facility as described before [ 32 ]. They were given nutritionally balanced commercial NIH31 diet.…”

“…They were given nutritionally balanced commercial NIH31 diet. The colony was propagated by heterozygous mating with PCR genotyping and no clinical or histological abnormalities were observed in IL10-null mice up to 10 weeks of age under our housing conditions [ 32 , 33 ]. IL10 null mice have no detectable IL10 expression.…”