Selenomethionine Suppressed TLR4/NF-κB Pathway by Activating Selenoprotein S to Alleviate ESBL Escherichia coli-Induced Inflammation in Bovine Mammary Epithelial Cells and Macrophages

Abstract

Inflammation is the hallmark of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli-induced bovine mastitis. Organic selenium can activate pivotal proteins in immune responses and regulate the immune system. The present study aimed to investigate whether selenomethionine (SeMet) attenuates ESBL E. coli-induced inflammation in bovine mammary epithelial cells (bMECs) and macrophages. Cells were treated with 0, 5/10, 10/20, 20/40, or 40/60 µM SeMet for 12 h and/or inoculated with ESBL-E. coli [multiplicity of infection (MOI) = 5] for 4/6 h, respectively. We assessed inflammatory responses, including selenoprotein S (SeS), Toll-like receptor 4 (TLR4), Ikappa-B (IκB), phospho-NF-κB p65 (Ser536), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and lactate dehydrogenase (LDH) activities. Treatment with 40/60 µM SeMet promoted cell viability and inhibited LDH activities in both bMECs and macrophages. Inoculation with ESBL-E. coli reduced cell viability, which was attenuated by SeMet treatment in bMECs and macrophages. SeMet increased ESBL E. coli-induced downregulation of SeS and decreased LDH activities, TLR4, IκB, phospho-NF-κB p65 (Ser536), IL-1β, and TNF-α protein expressions in bMECs and macrophages. In addition, knockdown of SeS promoted protein expression of TLR4mediated nuclear factor-kappa (NF-κB) pathway and BAY 11-708 inhibited TNF-α and IL-1β protein levels in bMECs and macrophages after ESBL-E. coli treatment. Moreover, ESBL-E. coli inoculation increased monocyte chemoattractant protein 1 (MCP-1), CC motif ligand 3 (CCL-3), and CCL-5 mRNA expressions in bMECs. In conclusion,

Immunomodulatory and Anti-Inflammatory Properties of Selenium-Containing Agents: Their Role in the Regulation of Defense Mechanisms against COVID-19

“…In addition, it reduces LPSinduced inflammation by inhibiting the NF-kB pathway, by enhancing the expression of selenoproteins, caspase 8, IkB-α, necroptosis markers (FADD, RIP1, RIP3, MLKL, and TNF-α), pro-inflammatory factors (NF-kB, PTGE, COX-2, iNOS, IL-1β, and IL-6), HSP60, HSP 70, and HSP 90. In addition, SLM modulates LPS-induced inhibition of the PI3K/AKT pathway and pro-inflammatory TLR4/NF-kb signaling pathway [104][105][106][107][108].…”

“…SLM modulation of the pro-inflammatory TLR4/NF-κB signaling pathway and macrophage activity was described in the study of inflammation of the mammary gland of cattle (mastitis) induced by E. coli. SLM attenuated inflammation caused by E. coli by modulating the transmission pathway signaling Toll-like receptor 4 (TLR4)/NF-κB and stimulated macrophages, enhancing their migration and activity [108].…”

TGF-β1 Signaling: Immune Dynamics of Chronic Kidney Diseases

“…It has been reported that TGF-β1 participated in macrophages-mediated immune dysfunction during the progression of CKD ( 15 , 141 , 142 ). TGF-β1 largely increases macrophages infiltration and accumulation in the injured kidney via stimulating the release of a potent cytokine for macrophages recruitment monocyte chemoattractant protein-1 (MCP-1) from various types of renal cells ( 143 – 145 ). TGF-β1 also regulates macrophage polarization and immunomodulatory cytokines secretion.…”

Toll-like receptor 4 agonist-based nanoparticles orchestrate protection against sepsis

“…The interactions between pathogen-associated molecular patterns (PAMPs), defined as highly conserved molecular structure in pathogenic microorganism, and pattern recognition receptors (PRRs) play an important role in the prevention and treatment of sepsis, including the recognition of infectious pathogens, the initiation of host inflammatory response and the activation of host immune defense [13][14][15]. Toll-like receptor (TLR) 4 activator, a typical PAMP with powerful biological functions, can regulate host inflammation, recruit granulocytes and macrophages to the infected sites and effectively promote pathogen clearance [16]. Furthermore, the insufficient activation of TLR4 signaling pathway in the host can promote the occurrence of infection and aggravate the progress of infection [1,17,18].…”