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

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 a (TNF-alpha) 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-alpha-exposed HPMECs. Moreover, LXA4 inhibited the phosphorylation and nuclear translocation of nuclear factor-kappa B/p65 (NF-kappa B/p65) and phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) in HPMECs following TNF-alpha stimulation. Heme oxygenase-1 (HO-1), a cytoprotective enzyme, was up-regulated by LXA4 in both non- and TNF-alpha-stimulated HPMECs. In conclusion, the protective effects of LXA4 to ALI may be executed through inhibition inflammation pathways of NF-kappa B and p38 MAPK and up-regulation of cytoprotective HO-1.

Lv, Chongqing (author)
Yu, Suhui (author)
Yang, Yunxiu (author)
Kong, Hongru (author)
Xie, Jianming (author)
Sun, Hongwei (author)
Andersson, RolandLund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)kir-ran (author)
Xu, Dan (author)
Chen, Bicheng (author)
Zhou, Mengtao (author)
Kirurgi, LundSektion V (creator_code:org_t)

In:Experimental Biology and Medicine: SAGE Publications238:12, s. 1388-13951535-37021535-3699

By the author/editor: Lv, Wanzhi; Lv, Chongqing; Yu, Suhui; Yang, Yunxiu; Kong, Hongru; Xie, Jianming; show more...; Sun, Hongwei; Andersson, Rolan ...; Xu, Dan; Chen, Bicheng; Zhou, Mengtao; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Surgery

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