Lipoxin A4 attenuation of endothelial inflammation response mimicking pancreatitis-induced lung injury

Abstract

Lipoxins (LXs) and their analogues are known to display potent anti-inflammatory actions. Previously, we reported that lipoxin A4 (LXA4) possessed powerful anti-inflammatory properties in acute pancreatitis in rats and that it may ameliorate the concomitant acute lung injury by reducing cytokine generation and inhibiting neutrophil activation. Considering that the vascular endothelium plays an important role during adherence, migration and activation of leukocytes, the present study was designed to investigate the effects of LXA4 on the inflammatory response induced by tumor necrosis factor α (TNF-α) in human pulmonary microvascular endothelial cells (HPMECs) and explore the potential mechanisms involved in these processes. We found that LXA4 markedly down-regulated the expression of monocyte chemotactic protein-1 (MCP-1), E-selectin, and interleukin-6 (IL-6) mRNA, as well as intercellular adhesion molecule-1 (ICAM-1) in TNF-α-exposed HPMECs. Moreover, LXA4 inhibited the phosphorylation and nuclear translocation of nuclear factor-κB/p65 (NF-κB/p65) and phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) in HPMECs following TNF-α stimulation. Heme oxygenase-1 (HO-1), a cytoprotective enzyme, was up-regulated by LXA4 in both non- and TNF-α-stimulated HPMECs. In conclusion, the protective effects of LXA4 to ALI may be executed through inhibition inflammation pathways of NF-κB and p38 MAPK and up-regulation of cytoprotective HO-1.

Emodin Ameliorates LPS-Induced Acute Lung Injury, Involving the Inactivation of NF-κB in Mice

“…MCP-1 was quickly up-regulated by many stimuli, such as oxidative stress, inflammation and shear forces, leading to the recruitment of more inflammatory cells, particularly neutrophils and macrophages, infiltrating into the damaged tissues [ 33 ]. Several studies confirmed that MCP-1 played a key role in the pathogenesis of ALI/ARDS, especially at the initial phase [ 34 , 35 ]. It has been proven that two kappa B binding sites are located in the transcriptional regulatory area of the MCP-1 gene [ 36 ].…”

The association between red blood cell distribution width and acute pancreatitis associated lung injury in patients with acute pancreatitis

“…And it was implied marks for severity and mortality of disease [14]. In addition, a large of laboratory tests associated with APALI were found in laboratory such as heme oxygenase start factor and lipid oxygen element A4 [15,16]. Nonetheless, those laboratory tests are rarely used in our clinical practice.…”

Lipoxin A4 Reduces Inflammation Through Formyl Peptide Receptor 2/p38 MAPK Signaling Pathway in Subarachnoid Hemorrhage Rats

“…6–8 LXA4 exerted these biological functions through down-regulating the activities of p38 mitogen-activated protein kinase (MAPK), which was mediated by FPR2. 7, 9, 10 Several studies have focused on the neuroprotective effects of LXA4 after stroke. Administration of LXA4 methyl ester was reported to reduce pro-inflammatory cytokines TNF-α and IL-1β and up-regulate anti-inflammatory cytokines IL-10 and TGF-β1 in the ischemic brain.…”