Staphylococcal-associated molecular patterns enhance expression of immune defense genes induced by IL-17 in mammary epithelial cells

Cytokine. 2011 Dec;56(3):749-59. doi: 10.1016/j.cyto.2011.09.020. Epub 2011 Oct 17.

Abstract

Interleukin-17A (IL-17A) and IL-17F have been shown to mediate a crucial crosstalk between the immune system and various epithelial tissues, stimulating various defensive mechanisms to bacterial infections. A number of studies have characterized the response to IL-17A and IL-17F of epithelial cells from airways, intestine, and skin, but not from the mammary gland. To evaluate the potential contribution of IL-17 to the immune defense of the mammary gland, we analyzed the effects of recombinant bovine IL-17A and IL-17F on primary bovine mammary epithelial cells (MEC) by quantitative PCR and ELISA. We found expression (mRNA) of the two components of the IL-17 receptor complex, IL-17RA and IL-17RC, in mammary tissue and MEC in vitro. The expression of a number of genes encoding cytokines, chemokines and proteins endowed with antibacterial activities was increased by IL-17A, and to a lesser extent by IL-17F, but the magnitude of responses was modest. As expected, responses were augmented by the combination of IL-17A or IL-17F with TNF-α. Interestingly, responses of a few of the tested genes, such as IL8, CCL20, iNOS, and CfB, were augmented by the combination of IL-17A with staphylococcal lipoteichoic acid or muramyl dipeptide, bacterial agonists of the innate immune system. This can be interpreted as indicating that IL-17A and IL-17F are tailored to exert their full potential in a septic environment. MEC responses were characterized by the expression of chemokines targeting not only neutrophils (CXCL3 and CXCL8) but also mononuclear leucocytes (CCL2, CCL20). Production of IL-6 was low and the inflammatory cytokines TNF-α and IL-1β were expressed (mRNA) but proteins were not secreted. Altogether, our results suggest that IL-17A and IL-17F have a potential to modulate the mammary gland immune response to mastitis-causing pathogens.

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / pharmacology
  • Animals
  • Cattle
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology*
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology*
  • Humans
  • Immunity / drug effects
  • Immunity / genetics*
  • Immunity, Innate / drug effects
  • Interleukin-17 / pharmacology*
  • Interleukin-8 / metabolism
  • Lipopolysaccharides / pharmacology
  • Mammary Glands, Animal / cytology*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-17 / genetics
  • Receptors, Interleukin-17 / immunology
  • Receptors, Pattern Recognition / immunology*
  • Staphylococcus / drug effects
  • Staphylococcus / immunology*
  • Teichoic Acids / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Interleukin-17
  • Interleukin-8
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Interleukin-17
  • Receptors, Pattern Recognition
  • Teichoic Acids
  • Tumor Necrosis Factor-alpha
  • Acetylmuramyl-Alanyl-Isoglutamine
  • lipoteichoic acid