Thrombin stimulates IL-6 and IL-8 expression in cytomegalovirus-infected human retinal pigment epithelial cells.
Recently, we reported that thrombin specifically stimulates protease-activated receptor-1 (PAR-1) signaling in RPE entailing inhibition of Sp1 dependent HCMV replication. We now studied whether thrombin modulates the expression of the proinflammatory cytokine/chemokines IL-6 and IL-8 in mock- and cytomegalovirus-infected human retinal pigment epithelial cells (RPE). Our data show that thrombin/PAR-1 stimulates IL-6 and IL-8 gene transcription and protein secretion in both mock- and HCMV-infected RPE. Thrombin/PAR-1-mediated signaling stimulated PKC and NF-kappaB-dependent IL-6 and IL-8 gene expression via phosphoinositide 3-kinase and further downstream via p42/44 and p38 MAPKs. Thus, thrombin/PAR-1-mediated IL-6/IL-8 gene expression is uncoupled from Sp1 inhibition and may support proinflammatory pathomechanisms probably involved in hemorrhage/HCMV retinitis progression.
Scholz
Martin
M
Institut für Medizinische Virologie, Zentrum der Hygiene, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Vogel
Jens-Uwe
JU
Höver
Gerold
G
Kotchetkov
Ruslan
R
Cinatl
Jaroslav
J
Doerr
Hans Wilhelm
HW
Cinatl
Jindrich
J
D003587:Cytomegalovirus / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D044463:Receptor, PAR-1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013917:Thrombin / Q000378:metabolism*
D015850:Interleukin-6; D016209:Interleukin-8; D044463:Receptor, PAR-1; D013917:Thrombin