Production of growth related oncogene protein-alpha in human umbilical vein endothelial cells stimulated with soluble interleukin-6 receptor-alpha: role of signal transducers, janus kinase 2 and mitogen-activated kinase kinase.
Growth-related oncogene protein-alpha (GRO-alpha) is a member of the C-X-C chemokine family with a wide variety of biological activities. We studied the production of GRO-alpha by human umbilical vein endothelial cells (HUVEC) in response to the stimulation with soluble form of interleukin-6 receptor alpha (sIL-6R). sIL-6R stimulated HUVEC to express GRO-alpha mRNA and secrete GRO-alpha protein in concentration-and time-dependent manners. The sIL-6R-induced GRO-alpha expression was inhibited by the pretreatment of the cells with AG490, a janus kinase 2 (JAK2) inhibitor, or with U0126, a MAP kinase-ERK kinase (MEK) inhibitor. sIL-6R also induced the phosphorylation of both Src homology 2-protein tyrosine phosphatase-2 (SHP-2), signal transducer and activator of transcription 3 (STAT3) and MEK. AG490 pretreatment inhibited the MEK phosphorylation but did not affect the STAT3 phosphorylation. We conclude that sIL-6R induces GRO-alpha expression in HUVEC through the activation of JAK2 and MEK.
Matsumiya
Tomoh
T
Department of Dentistry and Oral Surgery, Hirosaki University School of Medicine,Hirosaki 036-8562, Japan.
Imaizumi
Tadaatsu
T
Itaya
Hiroyuki
H
Shibata
Takeo
T
Yoshida
Hidemi
H
Sakaki
Hirotaka
H
Kimura
Hiroto
H
Satoh
Kei
K
D002478:Cells, Cultured; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D053614:Janus Kinase 2; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014471:Umbilical Veins / Q000166:cytology
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D020929:Mitogen-Activated Protein Kinase Kinases