Anti-inflammatory cytokine IL-10 and mammary gland development .

摘要

Background. IL-10 is an anti-inflammatory cytokine produced by Th2 T helper cells and it has pleiotropic effects in immunoregulation and inflammation. It inhibits the regulation of Th1 T helper cells, MHC class II expression on APC while enhancing B cell survival, proliferation and antibody production. IL-10 gene knockout studies in mice suggest that this cytokine is an important immunoregulator in intestinal tract. My first hypothesis is to test whether IL-10 suppresses breast cancer by regressing tumor sensitive areas such as TEBs by apoptosis. This was achieved by studying the mammary gland remodeling and its homeostasis at various cycles of estrus in D55 of both knockout and wildtype mice. My second hypothesis tested was whether IL-10 had any significant developmental changes in mammary gland of 2 day lactation group while observing for preneoplastic changes in the gland.;Methods. For the first hypothesis knockout and wildtype mice were sacrificed and the 4th & 5th pair of the mammary gland was used for wholemount and paraffin sections. Various developmental parameters such as mean area of WAT, total nuclei/field, outer half ductal area, outer half unbranched and branched TEBs, lymph node area and nipple to lymph node distance were measured.;For the second hypothesis, only the paraffin sections were analyzed for amount of glandular area vs. stromal area, average number of lobules per section, average number of acini per lobule per section, lobular complexity, and frequency of flattened nuclei, frequency of secretory differentiation, frequency of multilayered epithelium, and frequency of ducts present per section.;Results. Ablation of IL-10 show significantly decreased mammary gland homeostasis with respect to mean area of WAT, lymph node area and outer half unbranched TEBs. In 2 day lactation group, IL-10 has significantly decreased number of glandular area/field, glandular area/area of entire field, glandular area/stromal area and decreased lobular complexity. On the contrary, IL-10 has significantly increased number of cysts and stromal area/field as compared to wild type.