Bone Marrow Mesenchymal Stem Cells Combat Lipopolysaccharide-Induced Sepsis in Rats via Amendment of P38-MAPK Signaling Cascade

Abstract

Sepsis is a systemic inflammatory disorder which often occurs during extremely stressful conditions such as trauma, burn, shock, and infection. This study investigated the curative effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) against hepatic, renal, and pulmonary responses caused by a single administration of lipopolysaccharide (LPS) (10 mg/kg, i.p) in rats. Treatment with BM-MSCs (5 × 10 in 0.1 ml PBS, i.p.) 3 h after LPS antagonized the LPS-induced increment of the liver enzymes (ALT, AST) and kidney functions (BUN, sCr). BM-MSCs decreased tissue levels of P38-MAPK, NF-κB, STAT-3, TNF-α, IL-1β, iNOS, Bax together with elevation of the anti-inflammatory cytokine IL-10 and the anti-apoptotic biomarker Bcl-2. Meanwhile, rats exhibited marked reduction of the broncho-alveolar lavage fluid levels of TNF-α, IL-1β, and IFN-γ. Interestingly, BM-MSCs normalized both broncho-alveolar lavage fluid (BALF) neutrophils count and lung wet/dry ratios. Briefly, these findings may provide a preclinical platform for the management of LPS-induced sepsis using BM-MSCs via their ameliorative anti-inflammatory, anti-oxidant, and anti-apoptotic potentials.

Linkage of lncRNA CRNDE sponging miR-181a-5p with aggravated inflammation underlying sepsis

“…A number of pathways have been suggested to be sepsis related, including MAPK signaling, 31 tyrosine kinase-signaling and transcriptional activator signaling (JAK-STAT), 32 phosphatidylinositol 3-kinase/serine threonine protein kinase (PI3K/AKT) signaling 33 and glycogen synthase-3 (GSK-3) signaling. 33 Nevertheless, there has been scant evidence that verified the role of lncRNAs in sepsis, although over-expression of lncRNAs HOTAIR and MALAT1 were discovered in septic mouse models.…”

The effect of using kefir grains and mesenchymal stem cells in LPS-induced Alzheimer’s disease neuroinflammatory model

“…15 Also, bone marrow derived mesenchymal-mal Stem Cells (BM-MSCs) modulate anti-inflammatory immune response with alleviated Aβ aggregations and memory deficits in AD animals model. 16 As we mentioned, neurodegenerative diseases including AD are devastating disease that can be initiated from different stated conditions including inflammatory triggering factors. 17 Lipopolysaccharides (LPS) is the outer membrane of gram-negative bacteria which can be considered as one of the main stated AD neuroinflammatory initiatory factors in different subjects including rats by targeting toll-like receptor (TLR-4) leading to the propagation of series of inflammatory cascades using different downstream adaptors molecules and ending with a sever neuroinflammatoin in brain tissue resulting in the formation of AD neuroinflammatory type with enhanced Amyloid β and tangles formation.…”

l-Theanine alleviates heat stress-induced impairment of immune function by regulating the p38 MAPK signalling pathway in mice

“…21 p38 MAPK activates NF-κB and promotes its translocation into the nucleus, causing an inflammatory cascade, further amplifying the inflammatory immune response and aggravating tissue damage. 22,23…”

“…21 p38 MAPK activates NF-κB and promotes its translocation into the nucleus, causing an inflammatory cascade, further amplifying the inflammatory immune response and aggravating tissue damage. 22,23 L-Theanine, a characteristic amino acid in tea, is a glutamine compound. It is safe, non-toxic, and highly active, with a bioavailability of close to 100%.…”