A Novel Role of a Chemotherapeutic Agent in a Rat Model of Endotoxemia: Modulation of the STAT-3 Signaling Pathway

Abstract

Sepsis caused by lipopolysaccharide (LPS) is a life-threatening disease accompanied by multiple organ failure. This study investigated the curative effects of imatinib (IMA) against hepatic, renal, and pulmonary responses caused by a single administration of LPS (10 mg/kg, i.p.) in rats. Treatment with IMA (15 mg/kg, i.p.) 30 min after LPS antagonized the LPS-induced boost of liver enzymes (ALT, AST), kidney functions (BUN, sCr) as well as the elevated pulmonary vascular permeability and edema. IMA declined tissue contents of NF-κB, STAT-3, P38-MAPK, TNF-α, IL-1β, and iNOS. It also amplified the anti-inflammatory cytokine IL-10 as well as the Bcl-2/Bax ratio, a cardinal indicator of the anti-apoptotic effect. Meanwhile, the rats exhibited marked reduction of the broncho-alveolar lavage fluid (BALF) contents of TNF-α, IL-1β, IFN-γ, and neutrophil count; however, they revealed prominent augmentation of the BALF content IL-10. In conclusion, these findings suggest that IMA is endowed with anti-inflammatory, anti-oxidant, and anti-apoptotic properties and hence may provide a novel agent for the management of sepsis.

Effect of imatinib on lipopolysaccharide‑induced acute lung injury and endothelial dysfunction through P38 MAPK and NF-κB signaling pathway in vivo and in vitro

“…As previous studies only investigated p38 in IMA-treated sepsis rats [34], we further explored the rest proteins expressed in MAPK pathway in mouses and HUVECs. In the present study, IMA treatment inhibited the phosphorylation of P-38, Erk1/2, JNK of MAPKs in HUVECs and lung tissues.…”

Magnoliae flos Downregulated Lipopolysaccharide-Induced Inflammatory Responses via NF-κB/ERK-JNK MAPK/STAT3 Pathways

“…We assumed that it is caused by lack of time let the subjects under the stimuli ( Figure 2(d) and 5(c) ) [ 5 ]. Meanwhile, the representative endotoxin, LPS, triggers excessive production of the STAT protein family, specifically STAT3, which is associated with the upregulation of LPS-binding protein, causing an amplification of inflammation in sepsis [ 45 ]. We also found that MF suppressed signaling pathways in the nucleus and the cytosol in LPS-stimulated cells and mice (Figures 2 , 5 , and 6 ).…”

Cardiotrophin‐1 is an anti‐inflammatory cytokine and promotes IL‐4–induced M2 macrophage polarization

“…S3A-C). To understand the signaling pathway by which CT-1 suppresses LPSinduced inflammation, we investigated the activation of STAT-3, because LPS triggers excessive production of the STAT protein family, specifically STAT-3, which is involved in the up-regulation of LPS binding protein, leading to amplification of inflammation in sepsis (19). Western blotting analysis showed that LPS challenge increased the phosphorylation of STAT-3 in liver tissue, whereas CT-1 treatment attenuated these effects ( Fig.…”