Multifunctional cytokine expression by human coronary endothelium and regulation by monokines and glucocorticoids.
Human endothelium is capable of expressing a variety of molecules, including cytokines and growth factors, critical to inflammation. This aspect of coronary endothelium has not been studied in detail. In this study, we report, for the first time, expression of multifunctional cytokines by human coronary artery endothelial cells (HCAEC) and their regulation by inflammatory cytokines and glucocorticoids. We also compared expression of cytokine transcripts in two additional cell lines derived from pulmonary artery (HPAEC) and umbilical vein (HUVEC) endothelium. HCAEC expressed transcripts for interleukin 5 (IL-5), IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) constitutively. Induction of IL-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and MCP-1 was seen following treatment with TNFalpha. We found no expression of IL-1RA, IL-2, IL-4, IL-13, TNF-alpha, or IFN-gamma in HCAEC. IL-1beta and TNF-alpha synergistically induced IL-6 and GM-CSF and additively induced IL-8 and MCP-1 production, while IL-2, IL-10, IFN-alpha, and IFN-gamma had little or no additional effects. Interestingly, no IL-1alpha or IL-5 protein product was found even after maximal stimulation of HCAEC. No significant differences were seen in the profile of cytokine genes expressed by HCAEC, HPAEC, or HUVEC. Glucocorticoids inhibited IL-8 production from all three cell lines. This study demonstrates that human coronary endothelial cells are capable of expressing a wide variety of multifunctional cytokines which may be of relevance to vascular inflammation.
Krishnaswamy
G
G
Department of Medicine, East Tennessee State University, Johnson City, Tennessee 37614, USA.
Smith
J K
JK
Mukkamala
R
R
Hall
K
K
Joyner
W
W
Yerra
L
L
Chi
D S
DS
D002460:Cell Line; D019742:Chemokines, CC / Q000096:biosynthesis; D019743:Chemokines, CXC / Q000096:biosynthesis; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis; D015846:Monokines / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis
D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; D016898:Interferon-alpha; D016209:Interleukin-8; D015846:Monokines; D012333:RNA, Messenger; D003907:Dexamethasone