The role of TNF-alpha and its receptors in the production of beta-1,4-galactosyltransferase I mRNA by rat primary type-2 astrocytes.
beta-1,4-galactosyltransferase I (beta-1,4-GalT I) plays an important role in the synthesis of the backbone structure of adhesion molecules involved in leukocyte-endothelial cell interaction. The expression of beta-1,4-GalT I mRNA increased in primary human endothelial cells after exposure to tumor necrosis factor-alpha (TNF-alpha). In the central nervous system (CNS), astrocytes play a pivotal role in immunity as immunocompetent cells by secreting cytokines and inflammatory mediators, there are two types of astrocytes. Type-1 astrocytes can secrete TNF-alpha when stimulated with Lipopolysaccharide (LPS), while the responses of type-2 astrocytes during inflammation are unknown. So we examined the expression change of beta-1,4-GalT I mRNA in type-2 astrocytes after exposure to TNF-alpha and LPS. Real-time PCR showed that TNF-alpha or LPS affected beta-1,4-GalT I mRNA expression in a time- and dose-dependent manner. RT-PCR analysis revealed that TNFR1 and TNFR2 were present in normal untreated type-2 astrocytes, and that TNF-alpha, TNFR1 and TNFR2 increased in type-2 astrocytes after exposure to TNF-alpha or LPS. Immunocytochemistry showed that TNFR1 was expressed in the cytoplasm, nucleus and processes of normal untreated type-2 astrocytes, and distributed mainly in the cytoplasm and processes after exposure to LPS. TNFR2 was mainly expressed in the nucleus of normal untreated type-2 astrocytes, and distributed mainly in the processes of type-2 astrocytes after exposure to LPS. Both anti-TNFR1 and anti-TNFR2 antibodies suppressed beta-1,4-GalT I mRNA expression induced by TNF-alpha or LPS. From these results, we conclude that TNF-alpha signaling via both TNFR1 and TNFR2 translocated from nucleus to cytoplasm or processes is sufficient to induce beta-1,4-GalT I mRNA. In addition, we observed that not only exogenous TNF-alpha but also TNF-alpha produced by type-2 astrocytes affected beta-1,4-GalT I mRNA production in type-2 astrocytes. These results suggest that an autocrine loop involving TNF-alpha contributes to the production of beta-1,4-GalT I mRNA in response to inflammation.
Yan
Meijuan
M
Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qi-Xiu Road, Nantong, Jiangsu Province, 226001, P.R. China.
Xia
Chunlin
C
Niu
Shuqiong
S
Cheng
Chun
C
Shao
Xiaoyi
X
Shen
Aiguo
A
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D005700:Galactosyltransferases / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000906:Antibodies; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C506237:Tnfrsf1a protein, rat; D014409:Tumor Necrosis Factor-alpha; D005700:Galactosyltransferases; C119701:beta-1,4-galactosyltransferase I
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