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45. IL-1 regulation of transin/stromelysin transcription in rheumatoid synovial fibroblasts appears to involve two antagonistic transduction pathways, an inhibitory, prostaglandin-dependent pathway mediated by cAMP, and a stimulatory, protein kinase C-dependent pathway

Author

Case, J. P., Lafyatis, R., Kumkumian, G. K., Elaine F Remmers, and Wilder, R. L.

Subjects
Immunology, Immunology and Allergy
Abstract

IL-1, like other agents that have been shown a capacity to induce protein kinase C, is a potent transcriptional activator of the metalloproteinase, stromelysin, in synovial and other fibroblasts. cAMP has been shown to inhibit stromelysin transcription in fibroblasts of nonsynovial origin, and is regarded as an important second messenger for IL-1. In addition to stimulating metalloproteinase transcription, IL-1 also induces PGE2 production in synoviocytes. We determined that rIL-1 alpha led to the time-dependent accumulation of intracellular cAMP in serum-starved rheumatoid synovial fibroblasts, and that the effect was blocked by indomethacin. The cAMP agonists forskolin, 3-isobutyl-1-methylxanthine, and PGE2 suppressed the IL-1 induction of stromelysin; conversely, indomethacin superinduced IL-1-elicited stromelysin mRNA. These results were recapitulated on the transcriptional level in cells transfected with the rat transin/stromelysin promoter in a reporter (CAT) construct. 2',5'-Dideoxyadenosine, an inhibitor of adenylate cyclase, also augmented the IL-1 induction of stromeylsin mRNA, as did H-8, a specific inhibitor of the cAMP-dependent protein kinase A. Staurosporine and H-7, inhibitors of protein kinase C, blocked the IL-1 induction of stromelysin mRNA. We conclude that IL-1 appears to stimulate at least two transduction pathways in synovial fibroblasts from patients with rheumatoid arthritis, and that these have antagonistic effects on the regulation of stromelysin transcription.

Published
1990
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48. The epimorphin gene is highly conserved among humans, mice, and rats and maps to human chromosome 7, mouse chromosome 5, and rat chromosome 12.

Author

Zha, H, Remmers, E F, Szpirer, Claude, Szpirer, Josiane, Zhang, H, Kozak, C. A., Wilder, R L, Zha, H, Remmers, E F, Szpirer, Claude, Szpirer, Josiane, Zhang, H, Kozak, C. A., and Wilder, R L

Abstract

A genomic DNA fragment containing the rat epimorphin gene sequence was cloned from a rat DNA cosmid library using a mouse epimorphin cDNA probe. Within the cosmid insert, nine epimorphin exons were identified and sequenced. The predicted amino acid sequence of the rat epimorphin protein exhibited 96 and 86% identity with the mouse and human epimorphin proteins, respectively. Consistent with the developmentally related expression pattern of the mouse epimorphin gene, transcripts of the rat epimorphin gene were detected in 17-day postfertilization rat embryos. The gene, designated Epim, was assigned to rat chromosome 12 by somatic cell hybrid analysis and localized to 12q16 by fluorescence in situ hybridization. The mouse and human homologs of this gene were localized on mouse chromosome 5 and human chromosome 7 by linkage analysis and chromosomal in situ hybridization, respectively., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Published
1996

49. Linkage maps of rat chromosomes 15, 16, 17, 19, and X.

Author

Du, Yu, Remmers, E F, Goldmuntz, E A, Zha, H, Mathern, P, Ding, Y P, Kotake, S, Szpirer, Josiane, Szpirer, Claude, Wilder, R L, Du, Yu, Remmers, E F, Goldmuntz, E A, Zha, H, Mathern, P, Ding, Y P, Kotake, S, Szpirer, Josiane, Szpirer, Claude, and Wilder, R L

Abstract

Linkage maps of rat chromosomes 15, 16, 17, 19, and X were constructed by multipoint genetic linkage analysis of 22 polymorphic markers in 40 F2 progeny of Fischer (F344/N) and Lewis (LEW/N) inbred rat strains. These markers are associated with eight genes (angiotensin receptor A, M3 muscarinic acetylcholine receptor, heme oxygenase, endothelin receptor A, haptoglobin, tyrosine aminotransferase, phosphoribosylpyrophosphate synthetase subunit II, and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase) and 14 anonymous loci. Linkage analysis placed the markers into five linkage groups covering 11.7,7.9,11.6,42.5, and 5.1cM. These linkage groups were assigned to rat chromosomes 15, 16, 17, 19, and X, respectively, either by mouse x rat somatic cell hybrid analysis or based on previously identified locations of severalloci. In polymorphism analysis, these markers exhibited two to nine different alleles in 16 inbred rat strains., Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., info:eu-repo/semantics/published

Published
1996

50. A genetic map of microsatellite markers on rat chromosome 7.

Author

Du, Yu, Remmers, E F, Zha, H, Goldmuntz, E A, Szpirer, Josiane, Szpirer, Claude, Wilder, R L, Du, Yu, Remmers, E F, Zha, H, Goldmuntz, E A, Szpirer, Josiane, Szpirer, Claude, and Wilder, R L

Abstract

Nine microsatellite loci were mapped to rat Chromosome (Chr) 7 by genetic linkage and somatic cell hybrid analysis. These loci include the gene encoding a member of the IID sub-family of cytochrome P450 (Cyp2d), a gene with repetitive sequences expressed during myotube formation (D7Arb1e), four anonymous loci, D7Arb81, D7Arb208, D7Arb569, D7Arb609a, and three DNA loci defined by MapPair markers R245, R513, and R1071. The nine loci were all identified by PCR-based microsatellite polymorphism analysis and were characterized in 40 F2 intercross progeny of Fischer (F344/N) and Lewis (LEW/N) rats for segregation analysis. These markers formed a single linkage group spanning 76.8 cM with the following order and distances: D7Arb569-11.4 cM-D7Arb81-9.7 cM-R513-2.6 cM-Cyp2d-0.0 cM-R245-1.3 cM-D7Arb1e-10.4 cM-R1071-15.9 cM-D7Arb609a-15.4 cM-D7Arb208. Physical mapping of Cyp2d by somatic cell hybrid analysis allowed us to assign this linkage group to rat Chr 7. For each marker, two to six alleles were detected in a panel of 16 inbred rat strains (ACI/N, BN/SsN, BUF/N, DA/Bkl, F344/N, LER/N, LEW/N, LOU/MN, MNR/N, MR/N, SHR/N, SR/Jr, SS/Jr, WBB1/N, WBB2/N, WKY/N)., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
1995

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