Milk osteopontin regulates immune responses in mice stimulated by lipopolysaccharide (LPS)

Osteopontin (OPN) is a highly acidic phosphorylated glycoprotein. It is a pleiotropic protein and has been reported to be involved in a wide range of biological processes including initiation of immune responses, biomineralization, cell survival and cell proliferation. OPN appears in most bodily fluids and is present high concentration in human milk. However, the functions of milk OPN remain to be defined. OPN expression was found in mouse mammary glands and it is present at a high level in mouse milk. Therefore, mouse pups fed by wild type (control) or OPN knockout (OPN‐deficient group) dams were utilized to investigate functions of milk OPN on immune responses in early life. To examine effects of milk OPN on immune responses, mouse pups (D20, D30 and D40) were treated with an intraperitoneal injection of E. coli LPS, serotype O111:B4 (1.25 mg/kg, Sigma) in sterile saline. Mouse pups were then euthanized and plasma samples were collected for cytokine measurement (ELISA assays, R&D Systems) at different time points (0.5, 1, 2, 4, 8 & 24 h). Diarrhea symptoms were seen starting at 4 h and body weight was reduced by around 12.5% in all groups at 24 h. Plasma OPN and TNF‐α were significantly up‐regulated in both control and OPN‐deficient groups after LPS injection, but a considerably higher increase in plasma OPN and TNF‐α was observed in the OPN‐deficient group, indicating that milk OPN has anti‐inflammatory properties upon LPS administration. Similarly, plasma IFN‐γ was dramatically enhanced in response to the LPS challenge in both control and OPN‐deficient groups, but the control group showed a significantly higher increase in IFN‐γ. In conclusion, milk OPN may contribute to resistance to LPS administration (bacterial infection) by altering immune responses. Support or Funding Information Supported by Mead Johnson Nutrition.