Modulation of Bovine Endometrial Cell Receptors and Signaling Pathways as a Nanotherapeutic Exploration against Dairy Cow Postpartum Endometritis

Abstract

In order to control and prevent bovine endometritis, there is a need to understand the molecular pathogenesis of the infectious disease. Bovine endometrium is usually invaded by a massive mobilization of microorganisms, especially bacteria, during postpartum dairy cows. Several reports have implicated the Gram-negative bacteria in the pathogenesis of bovine endometritis, with information dearth on the potentials of Gram-positive bacteria and their endotoxins. The invasive bacteria and their ligands pass through cellular receptors such as TLRs, NLRs, and biomolecular proteins of cells activate the specific receptors, which spontaneously stimulates cellular signaling pathways like MAPK, NF-kB and sequentially triggers upregulation of pro-inflammatory cytokines. The cascade of inflammatory induction involves a dual signaling pathway; the transcription factor NF-κB is released from its inhibitory molecule and can bind to various inflammatory genes promoter. The MAPK pathways are concomitantly activated, leading to specific phosphorylation of the NF-κB. The provision of detailed information on the molecular pathomechanism of bovine endometritis with the interaction between host endometrial cells and invasive bacteria in this review would widen the gap of exploring the potential of receptors and signal transduction pathways in nanotechnology-based drug delivery system. The nanotherapeutic discovery of endometrial cell receptors, signal transduction pathway, and cell biomolecules inhibitors could be developed for strategic inhibition of infectious signals at the various cell receptors and signal transduction levels, interfering on transcription factors activation and pro-inflammatory cytokines and genes expression, which may significantly protect endometrium against postpartum microbial invasion.

Keywords: PAMP; biomolecules; cell receptors; cytokines; dairy cow; endometritis; nanosystem; nanotherapy; signaling pathways.

Figure 1

The mechanism of pathogen molecular recognition by Toll-like receptors triggering cellular signaling pathways activation (26,48). The mechanism of PAMP stimulating the cell receptor with their major transduction by biomolecules, which induced various isoforms of the signaling pathway and led to upregulation of pro-inflammatory cytokines and chemokines. The delivery of nanodrugs in suppressing inflammatory response in any part of the signaling pathways is essential in nanotherapeutic development against endometritis.

Figure 2

Intracellular Debugging of the NLR Signaling Pathways showing the cellular interconnectivity between PAMPs, cellular sensors, adaptors, and effectors to activate intracellular signaling cascade and stimulation of inflammation ultimate. The intracellular connections between its biomolecules are the basis for nanomedical and nanotechnology discovery against lingering subclinical endometritis.

Figure 3

Schematic diagram narrating the potential cascade of NF–κBand IKKαβ inhibitors to protect inflammatory gene.Table 88. Myeloid Differentiation factor 88.