Immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum

Colostrum provides essential nutrients and immunologically active factors that are beneficial to newborns. Our previous work demonstrated that milk contains large amounts of miRNA that is largely stored in milk-derived microvesicles (MVs). In the present study, we found that the MVs from colostrum contain significantly higher levels of several immune-related miRNAs. We hypothesized that the colostrum MVs may transfer the immune-related miRNAs into cells, which contribute to its immune modulatory feature. We isolated colostrum MVs by ultracentrifugation and demonstrated several immune modulation features associated with miRNAs. We also provide evidence that the physical structure of milk-derived MVs is essential for transfer miRNAs and following immune modulation effect. Moreover, we found that colostrum powder-derived MVs also contains higher levels of immune-related miRNAs that display similar immune modulation effects. Taken together, these results show that MV-containing immunerelated miRNAs may be a novel mechanism by which colostrum modulates body immune response.

[1]  W. Karmaus,et al.  Review: Immune Markers in Breast Milk and Fetal and Maternal Body Fluids: A Systematic Review of Perinatal Concentrations , 2011, Journal of human lactation : official journal of International Lactation Consultant Association.

[2]  A. Pivarcsi,et al.  MicroRNAs and immunity: novel players in the regulation of normal immune function and inflammation. , 2008, Seminars in cancer biology.

[3]  M. Kondolot,et al.  The effect of bovine colostrum on viral upper respiratory tract infections in children with immunoglobulin A deficiency , 2013, The clinical respiratory journal.

[4]  L. Isaac,et al.  Colostral Mononuclear Phagocytes are Able to Kill Enteropathogenic Escherichia coli Opsonized with Colostral IgA , 1997, Scandinavian journal of immunology.

[5]  Xiaolian Gao,et al.  Immune-related MicroRNAs are Abundant in Breast Milk Exosomes , 2011, International journal of biological sciences.

[6]  Jackeline Agorreta,et al.  microRNA-451 Regulates Macrophage Migration Inhibitory Factor Production and Proliferation of Gastrointestinal Cancer Cells , 2009, Clinical Cancer Research.

[7]  X. Chen,et al.  Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products , 2010, Cell Research.

[8]  M. L. Hastings,et al.  Selective Release of MicroRNA Species from Normal and Malignant Mammary Epithelial Cells , 2010, PloS one.

[9]  K. Vickers,et al.  MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins , 2011, Nature Cell Biology.

[10]  Hamid Cheshmi.  Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers , 2011 .

[11]  R. Monteiro,et al.  Colostral neutrophils express Fcα receptors (CD89) lacking γ chain association and mediate noninflammatory properties of secretory IgA , 2001, Journal of Leukocyte Biology.

[12]  X. Chen,et al.  Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA , 2011, Cell Research.

[13]  Jing Li,et al.  Secreted monocytic miR-150 enhances targeted endothelial cell migration. , 2010, Molecular cell.

[14]  Youchun Wang,et al.  Infection dynamics of hepatitis E virus in naturally infected pigs in a Chinese farrow-to-finish farm. , 2011, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[15]  Xianghuo He,et al.  microRNAs: tiny RNA molecules, huge driving forces to move the cell , 2010, Protein & Cell.

[16]  C. McCall,et al.  MicroRNAs regulatory networks in myeloid lineage development and differentiation: regulators of the regulators , 2012, Immunology and cell biology.

[17]  Riitta Lahesmaa,et al.  Exosomes with Immune Modulatory Features Are Present in Human Breast Milk1 , 2007, The Journal of Immunology.

[18]  V. Verhasselt,et al.  Mother to Child Transfer of IgG and IgA Antibodies Against Dermatophagoides pteronyssinus , 2011, Scandinavian journal of immunology.

[19]  R. Monteiro,et al.  Colostral neutrophils express Fc alpha receptors (CD89) lacking gamma chain association and mediate noninflammatory properties of secretory IgA. , 2001, Journal of leukocyte biology.

[20]  C. Wood,et al.  Resistance to Wheat streak mosaic virus generated by expression of an artificial polycistronic microRNA in wheat. , 2012, Plant biotechnology journal.

[21]  M. Kimura,et al.  Usefulness of Lymphocyte Stimulation Test for the Diagnosis of Intestinal Cow’s Milk Allergy in Infants , 2011, International Archives of Allergy and Immunology.

[22]  Yaosheng Chen,et al.  A deep investigation into the adipogenesis mechanism: Profile of microRNAs regulating adipogenesis by modulating the canonical Wnt/β-catenin signaling pathway , 2010, BMC Genomics.

[23]  Yong Huang,et al.  A study of miRNAs targets prediction and experimental validation , 2010, Protein & Cell.

[24]  N. Aoki,et al.  Isolation of bovine milk-derived microvesicles carrying mRNAs and microRNAs. , 2010, Biochemical and biophysical research communications.

[25]  Johan Skog,et al.  Glioblastoma microvesicles transport RNA and protein that promote tumor growth and provide diagnostic biomarkers , 2008, Nature Cell Biology.

[26]  X. Chen,et al.  Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases , 2008, Cell Research.

[27]  N. Kosaka,et al.  microRNA as a new immune-regulatory agent in breast milk , 2010, Silence.

[28]  Samir K. Brahmachari,et al.  Posttranscriptional regulation of interleukin-10 expression by hsa-miR-106a , 2009, Proceedings of the National Academy of Sciences.

[29]  X. Wang,et al.  Novel therapeutic Strategies for Targeting Liver Cancer Stem Cells , 2011, International journal of biological sciences.