IL-8 induces imbalances between nitric oxide and endothelin-1, and also between plasminogen activator inhibitor-1 and tissue-type plasminogen activator in cultured endothelial cells.
Interleukin-8 (IL-8), a member of the CXC chemokine family, plays an important role in the modulation of multiple biological functions in endothelial cells containing the receptors CXCR1 and CXCR2. It has previously been shown that IL-8 directly enhances endothelial cell survival, and stimulates the production of matrix metalloproteinases, which in turn regulates angiogenesis. However, its role in the regulation of the production of vasoactive substances in endothelial cells is less well defined. In this study, we investigate the effects of IL-8 on the proliferation of human umbilical vein endothelial cells (HUVECs). In addition, we also study the effects of IL-8 on the production of vasodilator, vasoconstrictor and fibrinolytic factors in these cells. The results show that recombinant IL-8 (50-200ng/ml) induces neither HUVEC proliferation nor nitric oxide (NO) release. However, it significantly increases the production of endothelin-1 (ET-1) in a concentration-dependent manner. Furthermore, incubation of endothelial cells with IL-8 (200ng/ml) up-regulates the plasminogen activator inhibitor-1 (PAI-1) in HUVECs, while it down-regulates the tissue plasminogen activator (t-PA). These findings suggest that IL-8 offsets the balance between endothelial vasoconstrictors and vasodilators. Furthermore, IL-8 also leads to an imbalance between PAI-1 and t-PA, which causes the ECs to become procoagulative and hypofibrinolytic.
Cheng
Min
M
Laboratory of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
Li
Yi
Y
Wu
Jiang
J
Nie
Yongmei
Y
Li
Liang
L
Liu
Xiaojing
X
Charoude
Hojjatollah Nozad
HN
Chen
Huaiqing
H
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D019332:Endothelin-1 / Q000096:biosynthesis*; D005343:Fibrinolytic Agents / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis*; D014662:Vasoconstrictor Agents / Q000378:metabolism; D014665:Vasodilator Agents / Q000378:metabolism
C508606:CXCL8 protein, human; D019332:Endothelin-1; D005343:Fibrinolytic Agents; D016209:Interleukin-8; D017395:Plasminogen Activator Inhibitor 1; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D011994:Recombinant Proteins; C051321:SERPINE1 protein, human; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D010959:Tissue Plasminogen Activator; D017364:Collagenases