Cytochemical alterations in the rat retina by LPS administration.
LPS-induced inflammation and changes in protein phosphorylation and the JAK-STAT pathway accompanying glial activation after LPS treatment, were followed by analyzing secreted proinflammatory cytokine levels. The administration of LPS caused tyrosine phosphorylation of STAT3 in retinae and induced glial fibrillary acidic protein. (GFAP) from the nerve fiber layer to the ganglion cell layer. Our results suggest that the LPS-induced activation of the JAK2/STAT3 signaling pathway may play a key role in the induction of astrogliosis. However, no significant increase in vimentin, OX-42 or inducible nitric oxide synthase (iNOS) expressions were observed after LPS administration. Sphingosine kinase catalyzes the conversion of sphingosine to sphingosine-1-phosphate (So-1-P), a sphingolipid metabolite that plays important roles in angiogenesis, inflammation, and cell growth. In the present study, it was found that sphingolipid metabolite levels were elevated in the serum and retinae of LPS-injected rats. To further investigate the chronic effect of increased So-1-P in the retina, So-1-P was infused intracerebroventricularly (i.c.v.) into rats using an osmotic minipump at 100 pmol/10 microl h(-1) for 7 days, and was found to increase retinal GFAP expression. These observations suggest that LPS induces the activation of retinal astrocytes via JAK2/STAT3 and that LPS affects So-1-P generation. Our findings also suggest that elevated So-1-P in the retina and/or in serum could induce cytochemical alterations in LPS treated or inflamed retinae.
Jang
Soyong
S
Department of Neuroscience and Medical Research Institute, College of Medicine, Ewha Womans University, Seoul 158-710, Korea.
Lee
Jae-Hyung
JH
Choi
Kyu-Ryong
KR
Kim
Donghyun
D
Yoo
Hwan-Soo
HS
Oh
Seikwan
S
D000818:Animals; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007276:Injections, Intraventricular; D053583:Interleukin-1beta / Q000378:metabolism; D053613:Janus Kinase 1 / Q000096:biosynthesis; D053614:Janus Kinase 2 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008246:Lysophospholipids / Q000494:pharmacology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000096:biosynthesis; D050795:STAT2 Transcription Factor / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013107:Sphingolipids / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014746:Vimentin / Q000096:biosynthesis
D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008246:Lysophospholipids; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D050796:STAT3 Transcription Factor; D013107:Sphingolipids; C494081:Stat1 protein, rat; C494088:Stat3 protein, rat; D014409:Tumor Necrosis Factor-alpha; D014746:Vimentin; C060506:sphingosine 1-phosphate; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D013110:Sphingosine