title: Sodium Octanoate Modulates the Innate Immune Response of Bovine Mammary Epithelial Cells through the TLR2/P38/JNK/ERK1/2 Pathway: Implications duringStaphylococcus aureusInternalization.
abstract: Bovine mammary epithelial cells (bMECs) contribute to mammary gland defense against invading pathogens, such asStaphylococcus aureus(intracellular facultative), which is recognized by TLR2. In a previous report, we showed that sodium octanoate [NaO, a medium chain fatty acid (C8)] induces (0.25 mM) or inhibits (1 mM)S. aureusinternalization into bMECs and differentially regulates the innate immune response (IIR). However, the molecular mechanisms have not been described, which was the aim of this study. The results showed that α5β1 integrin membrane abundance (MA) was increased in 0.25 mM NaO-treated cells, but TLR2 or CD36 MA was not modified. When these receptors were blocked individually, 0.25 mM NaO-increasedS. aureusinternalization was notably reduced. Interestingly, in this condition, the IIR of the bMECs was impaired because MAPK (p38, JNK, and ERK1/2) phosphorylation and the activation of transcription factors related to these pathways were decreased. In addition, the 1 mM NaO treatment induced TLR2 MA, but neither the integrin nor CD36 MA was modified. The reduction inS. aureusinternalization induced by 1 mM NaO was increased further when TLR2 was blocked. In addition, the phosphorylation levels of the MAPKs increased, and 13 transcriptional factors related to the IIR were slightly activated (CBF, CDP, c-Myb, AP-1, Ets-1/Pea-3, FAST-1, GAS/ISRE, AP-2, NFAT-1, OCT-1, RAR/DR-5, RXR/DR-1, and Stat-3). Moreover, the 1 mM NaO treatment up-regulated gene expression of IL-8 and RANTES and secretion of IL-1β. Notably, when 1 mM NaO-treated bMECs were challenged withS. aureus, the gene expression of IL-8 and IL-10 increased, while IL-1β secretion was reduced. In conclusion, our results showed that α5β1 integrin, TLR2 and CD36 are involved in 0.25 mM NaO-increasedS. aureusinternalization in bMECs. In addition, 1 mM NaO activates bMECs via the TLR2 signaling pathways (p38, JNK, and ERK1/2), which improves IIR beforeS. aureusinvasion. Additionally, NaO (1 mM) might exert anti-inflammatory effects after bacterial internalization.
authors.affiliation: Licenciatura en Genómica Alimentaria, Universidad de La Ciénega del Estado de Michoacán de Ocampo Sahuayo, Mexico.
authors.forename: Nayeli
authors.initials: N
authors.lastname: Alva-Murillo
authors.affiliation: Facultad de Medicina Veterinaria y Zootecnia, Centro Multidisciplinario de Estudios en Biotecnología, Universidad Michoacana de San Nicolás de Hidalgo Morelia, Mexico.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ochoa-Zarzosa
authors.affiliation: Facultad de Medicina Veterinaria y Zootecnia, Centro Multidisciplinario de Estudios en Biotecnología, Universidad Michoacana de San Nicolás de Hidalgo Morelia, Mexico.
authors.forename: Joel E
authors.initials: JE
authors.lastname: López-Meza
mesh_terms: D000818:Animals; D002210:Caprylates / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004705:Endocytosis; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects*; D007155:Immunologic Factors / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D013211:Staphylococcus aureus / Q000276:immunology / Q000502:physiology*
chemical_list: D002210:Caprylates; D007155:Immunologic Factors; C031492:octanoic acid
keywords: Staphylococcus aureus; TLR2; epithelial cells; inflammatory response; internalization; octanoate