TRDMT1 exhibited protective effects against LPS‐induced inflammation in rats through TLR4‐NF‐κB/MAPK‐TNF‐α pathway

Abstract

Background Inflammation is a complex physiological and pathological process. Although many types of inflammation are well characterized, their physiological functions are largely unknown. tRNA aspartic acid methyltransferase 1 (TRDMT1) has been implicated as a stress‐related protein, but its intrinsic biological role is unclear. Methods We constructed a Trdmt1 knockout rat and adopted the LPS‐induced sepsis model. Survival curve, histopathological examination, expression of inflammatory factors, and protein level of TLR4 pathway were analyzed. Results Trdmt1 deletion had no obvious impact on development and growth. Trdmt1 deletion slightly increased the mortality during aging. Our data showed that Trdmt1 strongly responded in LPS‐treated rats, and Trdmt1 knockout rats were vulnerable to LPS treatment with declined survival rate. We also observed more aggravated tissue damage and more cumulative functional cell degeneration in LPS‐treated knockout rats compared with control rats. Further studies showed upregulated TNF‐α level in liver, spleen, lung, and serum tissues, which may be explained by enhanced p65 and p38 phosphorylation. Conclusions Our data demonstrated that Trdmt1 plays a protective role in inflammation by regulating the TLR4‐NF‐κB/MAPK‐TNF‐α pathway. This work provides useful information to understand the TRDMT1 function in inflammation.

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“…LPS‐induced inflammation involves several cell types such as lymphocytes, macrophages, and granulocytes 3 . Activation of immune responses is associated with production of multiple pro‐inflammatory cytokines and adhesion molecules which have detrimental effects on several organs 2–4 . LPS‐induced systemic inflammation has also been shown to disturb endothelial vascular homeostasis with subsequent irreversible cardiac dysfunction 3 …”

“…Sepsis is characterized by inflammatory responses to infection and can be lead to death in critically ill individuals 1 . Activation of innate immunity and inflammatory responses by lipopolysaccharide (LPS), the main pathogenic factor of gram‐negative bacteria, is responsible for the organ damage 2 . The stimulation of Toll‐like receptor‐4 by LPS results in activation of nuclear factor kappa ß (NF‐kß).…”

“…The stimulation of Toll‐like receptor‐4 by LPS results in activation of nuclear factor kappa ß (NF‐kß). NF‐𝜅B regulates the expression of multiple inflammatory mediators 2–4 . LPS can directly trigger some acute inflammatory responses in endothelial cells including release of vascular cell adhesion molecule‐1, E‐selectin, intercellular adhesion molecule‐1, pro‐inflammatory cytokines (such as tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐6), and monocyte chemoattractant protein‐1.…”

“…1 Activation of innate immunity and inflammatory responses by lipopolysaccharide (LPS), the main pathogenic factor of gram-negative bacteria, is responsible for the organ damage. 2 The stimulation of Toll-like receptor-4 by LPS results in activation of nuclear factor kappa ß (NF-kß). NF-𝜅B regulates the expression of multiple inflammatory mediators.…”

“…NF-𝜅B regulates the expression of multiple inflammatory mediators. [2][3][4] LPS can directly trigger some acute inflammatory responses in endothelial cells including release of vascular cell adhesion molecule-1, E-selectin, intercellular adhesion molecule-1, pro-inflammatory cytokines (such as tumor necrosis factorα (TNFα), interleukin (IL)-6), and monocyte chemoattractant protein-1. During sepsis, systemic inflammation is regarded as a necessary host-defense response to pathogens.…”