Low intensity shear stress increases endothelial ELR+ CXC chemokine production via a focal adhesion kinase-p38{beta} MAPK-NF-{kappa}B pathway.
CXC chemokines with a glutamate-leucine-arginine (ELR) tripeptide motif (ELR(+) CXC chemokines) play an important role in leukocyte trafficking into the tissues. For reasons that are not well elucidated, circulating leukocytes are recruited into the tissues mainly in small vessels such as capillaries and venules. Because ELR(+) CXC chemokines are important mediators of endothelial-leukocyte interaction, we compared chemokine expression by microvascular and aortic endothelium to investigate whether differences in chemokine expression by various endothelial types could, at least partially, explain the microvascular localization of endothelial-leukocyte interaction. Both in vitro and in vivo models indicate that ELR(+) CXC chemokine expression is higher in microvascular endothelium than in aortic endothelial cells. These differences can be explained on the basis of the preferential activation of endothelial chemokine production by low intensity shear stress. Low shear activated endothelial ELR(+) CXC chemokine production via cell surface heparan sulfates, beta(3)-integrins, focal adhesion kinase, the mitogen-activated protein kinase p38beta, mitogen- and stress-associated protein kinase-1, and the transcription factor.
Shaik
Sadiq S
SS
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35233, USA.
Soltau
Thomas D
TD
Chaturvedi
Gaurav
G
Totapally
Balagangadhar
B
Hagood
James S
JS
Andrews
William W
WW
Athar
Mohammad
M
Voitenok
Nikolai N
NN
Killingsworth
Cheryl R
CR
Patel
Rakesh P
RP
Fallon
Michael B
MB
Maheshwari
Akhil
A
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D015153:Blotting, Western; D019743:Chemokines, CXC / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D039641:Integrin beta Chains / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D055806:Microvessels / Q000502:physiology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010957:Plasmids; D034622:RNA Interference; D051381:Rats; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical; D013552:Swine; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism
D019743:Chemokines, CXC; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006497:Heparan Sulfate; D039641:Integrin beta Chains; D008156:Luciferases; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048051:p38 Mitogen-Activated Protein Kinases; D054460:rho-Associated Kinases; C116919:mitogen and stress-activated protein kinase 1