Tilmicosin modulates the innate immune response and preserves casein production in bovine mammary alveolar cells duringStaphylococcus aureusinfection1

Abstract

Tilmicosin is an antimicrobial agent used to treat intramammary infections against Staphylococcus aureus and has clinical anti-inflammatory effects. However, the mechanism by which it modulates the inflammatory process in the mammary gland is unknown. We evaluated the effect of tilmicosin treatment on the modulation of the mammary innate immune response after S. aureus infection and its effect on casein production in mammary epithelial cells. To achieve this goal, we used immortalized mammary epithelial cells (MAC-T), pretreated for 12 h or treated with tilmicosin after infection with S. aureus (ATCC 27543). Our data showed that tilmicosin decreases intracellular infection (P < 0.01) and had a protective effect on MAC-T reducing apoptosis after infection by 80% (P < 0.01). Furthermore, tilmicosin reduced reactive oxygen species (ROS) (P < 0.01), IL-1β (P < 0.01), IL-6 (P < 0.01), and TNF-α (P < 0.05) production. In an attempt to investigate the signaling pathways involved in the immunomodulatory effect of tilmicosin, mitogen-activated protein kinase (MAPK) phosphorylation was measured by fluorescent-activated cell sorting. Pretreatment with tilmicosin increased ERK1/2 (P < 0.05) but decreased P38 phosphorylation (P < 0.01). In addition, the anti-inflammatory effect of tilmicosin helped to preserve casein synthesis in mammary epithelial cells (P < 0.01). This result indicates that tilmicosin could be an effective modulator inflammation in the mammary gland. Through regulation of MAPK phosphorylation, ROS production and pro-inflammatory cytokine secretion tilmicosin can provide protection from cellular damage due to S. aureus infection and help to maintain normal physiological functions of the bovine mammary epithelial cell.

Synthesis of Tilmicosin Nanostructured Lipid Carriers for Improved Oral Delivery in Broilers: Physiochemical Characterization and Cellular Permeation

“…Tilmicosin, derived from tylosin, is a bacteriostatic broad-spectrum macrolide antibiotic that has a wide range of veterinary uses, including treatment of bacterial and Mycoplasma infections (such as pulmonary infection) through inhibiting the biosynthesis of microbial protein. It has also been recently used to treat mastitis [1,2]. Previously, tilmicosin was approved to treat Pasteurella infection in swine and bovines and also control Mycoplasma infection in chickens [3].…”

Enhanced Treatment Effects of Tilmicosin Against Staphylococcus aureus Cow Mastitis by Self-Assembly Sodium Alginate-Chitosan Nanogel

“…It was proved that administrating tilmicosin to cows at a dosage of 20 mg/kg by subcutaneous was useful for the treatment of intramammary infections caused by S. aureus [10]. Meanwhile, Martínez-Cortés et al proved that tilmicosin could be used as an effective modulator of inflammation in the mammary gland, since tilmicosin could prevent cells from being damaged and help to maintain normal physiological functions of the cow mammary epithelial cell [11]. According to reports, the typical characteristics of S. aureus cow mastitis are chronic infection and reinfection [12,13].…”

Pharmacokinetics of tilmicosin in plasma, urine and feces after a single intragastric administration in donkey (Equus asinus)

“…Tilmicosin is a macrolide antibiotic developed in the 1980s as a broad‐spectrum antimicrobial in veterinary clinical practice (Martínez‐Cortés et al., 2019; Villarino & Martín‐Jiménez, 2013). It can irreversibly bind to the 50S subunit of bacterial ribosomes and selectively inhibit protein synthesis by blocking transpeptidation and mRNA displacement (Vázquez‐Laslop & Mankin, 2018).…”