JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2014, Vol. 52 ›› Issue (10): 15-19.doi: 10.6040/j.issn.1671-7554.0.2014.351

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LPS induces lung angiogenesis via PGE2-EP2 pathway in mouse model

ZHANG Pengfei, XU Xiaoya, JIANG Man, BI Yuli, XU Jiying, HAN Mingyong   

  1. Cancer Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
  • Received:2014-05-30 Revised:2014-09-19 Online:2014-10-10 Published:2014-10-10

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Abstract: Objective To investigate the mechanism by which Lipopolysaccharide (LPS) induced angiogenesis in mice lungs. Methods Twelve female BALB/c mice aged 6 to 8 weeks were divided into LPS and PBS groups randomly, which were intraperitoneally injected into LPS and PBS, respectively. Lung tissues were collected to determine the pulmonary blood vessel density by HE staining and CD31 immunofluorescence staining. Vascular endothelial growth factor (VEGF) level in serum of all mice were assayed by ELISA. Mouse pulmonary vascular endothelial cells (MPVECs) were stimulated with VEGF, PGE2, Celecoxib, EP receptor inhibitor AH6809 and EP receptor agonists (ONO-AE1-259-01, ONO-DI-004, ONO-AE-248, and ONO-AE1-329). Then culture supernatant was collected to assay VEGF expression and tube forming test was performed to observe angiogenesis of endothelial cells. Results LPS induced inflammatory response and angiogenesis in mice lungs. Serum VEGF level of LPS treated mice were higher than those of PBS treated mice (P<0.01). VEGF or PGE2 used separately could increase angiogenesis. Celecoxib reduced VEGF levels released by MPVECs and suppressed angiogenesis. VEGF production was increased by ONO-AE1-259-01 (P<0.05) and decreased by AH6809 (P<0.05). Other EP receptor agonists had no significant effects on VEGF production. Conclusion LPS can induce inflammatory response in mice lungs, and increase serum VEGF level. Celecoxib can counteract this effect. LPS promotes angiogenesis by increasing the production of VEGF via PGE2-EP2 pathway.

Key words: PGE2-EP2 pathway, Angiogenesis, Lipopolysaccharide, Animal model

CLC Number: 

  • R734.2
[1] Ikebe M, Kitaura Y, Nakamura M, et al. Lipopolysaccharide (LPS) increases the invasive ability of pancreatic cancer cells through the TLR4/MyD88 signaling pathway[J]. J Surg Oncol, 2009, 100(8):725-731.
[2] He Z, Zhu Y, Jiang H. Inhibiting toll-like receptor 4 signaling ameliorates pulmonary fibrosis during acute lung injury induced by lipopolysaccharide: an experimental study[J]. Respir Res, 2009, 10: 126.
[3] Valcárcel M, Mendoza L, Hernández J J, et al. Vascular endothelial growth factor regulates melanoma cell adhesion and growth in the bone marrow microenvironment via tumor cyclooxygenase-2[J]. J Transl Med, 2011, 9: 142.
[4] Zhao Y, Kong X, Li X, et al. Metadherin mediates lipopolysaccharide-induced migration and invasion of breast cancer cells[J]. PLoS One, 2011, 6(12): e29363. doi: 10.1371/journal.pone.0029363.
[5] Attar B M, George M, Ion-Nedelcu N, et al. Disease dependent qualitative and quantitative differences in the inflammatory response to ascites occurring in cirrhotics[J]. World J Hepatol, 2014, 6(2): 85-91.
[6] Baeriswyl V, Christofori G. The angiogenic switch in carcinogenesis[J]. Semin Cancer Biol, 2009, 19(5): 329-337.
[7] 徐晓娅, 毕玉莉, 姜曼, 等.血管内皮生长因子促进肺转移相关受体通路的研究[J].山东大学学报:医学版, 2013, 51(11): 25-29. XU Xiaoya, BI Yuli, JIANG Man, et al. Vascular endothelial growth factor (VEGF) promotes lung carcinoma metastasis via VEGFR1 in mouse model[J]. Journal of Shandong University: Health Sciences, 2013, 51(11): 25-29.
[8] Ranganathan P V, Jayakumar C, Mohamed R, et al. Netrin-1 regulates the inflammatory response of neutrophils and macrophages, and suppresses ischemic acute kidney injury by inhibiting COX-2-mediated PGE2 production[J]. Kidney Int, 2013, 83(6): 1087-1098.
[9] Weems Y S, Bridges P J, Jeoung M, et al. In vivo intra-luteal implants of prostaglandin (PG) E1 or E2 (PGE1, PGE2) prevent luteolysis in cows. Ⅱ: mRNA for PGF2α, EP1, EP2, EP3 (AD), EP3A, EP3B, EP3C, EP3D, and EP4 prostanoid receptors in luteal tissue[J]. Prostaglandins Other Lipid Mediat, 2012, 97(1-2): 60-65.
[10] Morita Y, Morita N, Hata K, et al. Cyclooxygenase-2 expression is associated with vascular endothelial growth factor-c and lymph node metastasis in human oral tongue cancer[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2014, 117(4): 502-510.
[11] Frölich S, Olliges A, Kern N, et al. Temporal expression of the PGE2 synthetic system in the kidney is associated with the time frame of renal developmental vulnerability to cyclooxygenase-2 inhibition[J]. Am J Physiol Renal Physiol, 2012, 303(2): F209-F219.
[12] Peng M, Wang Y L, Wang F F, et al. The cyclooxygenase-2 inhibitor parecoxib inhibits surgery-induced proinflammatory cytokine expression in the hippocampus in aged rats[J]. J Surg Res, 2012, 178(1): e1-e8. doi: 10.1016/j.jss.2012.08.030.
[13] Zhao L, Wu Y, Xu Z, et al. Involvement of COX-2/PGE2 signalling in hypoxia-induced angiogenic response in endothelial cells[J]. J Cell Mol Med, 2012, 16(8): 1840-1855.
[14] Wang X, Li G, Wang A, et al. Combined histone deacetylase and cyclooxygenase inhibition achieves enhanced antiangiogenic effects in lung cancer cells[J]. Mol Carcinog, 2013, 52(3): 218-228.
[15] Nakanishi M, Sato T, Li Y, et al. Prostaglandin E2 stimulates the production of vascular endothelial growth factor through the E-prostanoid-2 receptor in cultured human lung fibroblasts[J]. Am J Respir Cell Mol Biol, 2012, 46(2): 217-223.
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