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Interleukin-1 beta induction of tissue inhibitor of metalloproteinase (TIMP-1) is functionally antagonized by prostaglandin E2 in human synovial fibroblasts.
J Cell Biochem. 1995 Apr; 57(4):619-29.JC

Abstract

Elevated levels of tissue inhibitor of metalloproteases-1 (TIMP-1) have been demonstrated in inflamed synovial membranes, and it is believed that the inhibitor may play a critical role in the regulation of connective tissue degradation. The present study was undertaken to define the cellular mechanism of action of the inflammatory mediators, interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2), in the control of TIMP-1 synthesis and expression in human synovial fibroblasts. Recombinant human IL-1 beta induced a time- and dose-dependent saturable response in terms of TIMP-1 mRNA expression (effective concentration for 50% maximal response, EC50 = 31.5 +/- 3.3 pg/ml) and protein synthesis (EC50 = 30 +/- 3.3 pg/ml). The protein kinase C (PKC) inhibitors, H-7, staurosporine, and calphostin C, reversed the rhIL-1 beta induction of TIMP-1 mRNA. PGE2 also inhibited rhIL-1 beta-stimulated TIMP-1 mRNA expression and protein secretion in a dose-dependent fashion. The concentration of PGE2 necessary to block 50% of rhIL-1 beta-stimulated TIMP-1 secretion, IC50, was 1.93 ng/ml (4.89 nM). Forskolin, and other stable derivatives of cAMP, mimicked, to a large extent, the effects of PGE2. The phorbol ester, PMA, up-regulated considerably the mRNA expression of TIMP-1 but had no effect on protein production. Calphostin C substantially reduced PMA-activated TIMP-1 expression. Staurosporine, calphostin C, H-7, and substances that elevate cellular levels of cAMP, like PGE2, also reduced basal expression and synthesis of TIMP-1. Taken together, the data suggest that PKA and C may mediate opposing effects in terms of TIMP-1 expression and secretion in human synovial fibroblasts.

Authors+Show Affiliations

University of Montreal, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7615646

Citation

DiBattista, J A., et al. "Interleukin-1 Beta Induction of Tissue Inhibitor of Metalloproteinase (TIMP-1) Is Functionally Antagonized By Prostaglandin E2 in Human Synovial Fibroblasts." Journal of Cellular Biochemistry, vol. 57, no. 4, 1995, pp. 619-29.
DiBattista JA, Pelletier JP, Zafarullah M, et al. Interleukin-1 beta induction of tissue inhibitor of metalloproteinase (TIMP-1) is functionally antagonized by prostaglandin E2 in human synovial fibroblasts. J Cell Biochem. 1995;57(4):619-29.
DiBattista, J. A., Pelletier, J. P., Zafarullah, M., Iwata, K., & Martel-Pelletier, J. (1995). Interleukin-1 beta induction of tissue inhibitor of metalloproteinase (TIMP-1) is functionally antagonized by prostaglandin E2 in human synovial fibroblasts. Journal of Cellular Biochemistry, 57(4), 619-29.
DiBattista JA, et al. Interleukin-1 Beta Induction of Tissue Inhibitor of Metalloproteinase (TIMP-1) Is Functionally Antagonized By Prostaglandin E2 in Human Synovial Fibroblasts. J Cell Biochem. 1995;57(4):619-29. PubMed PMID: 7615646.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-1 beta induction of tissue inhibitor of metalloproteinase (TIMP-1) is functionally antagonized by prostaglandin E2 in human synovial fibroblasts. AU - DiBattista,J A, AU - Pelletier,J P, AU - Zafarullah,M, AU - Iwata,K, AU - Martel-Pelletier,J, PY - 1995/4/1/pubmed PY - 1995/4/1/medline PY - 1995/4/1/entrez SP - 619 EP - 29 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 57 IS - 4 N2 - Elevated levels of tissue inhibitor of metalloproteases-1 (TIMP-1) have been demonstrated in inflamed synovial membranes, and it is believed that the inhibitor may play a critical role in the regulation of connective tissue degradation. The present study was undertaken to define the cellular mechanism of action of the inflammatory mediators, interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2), in the control of TIMP-1 synthesis and expression in human synovial fibroblasts. Recombinant human IL-1 beta induced a time- and dose-dependent saturable response in terms of TIMP-1 mRNA expression (effective concentration for 50% maximal response, EC50 = 31.5 +/- 3.3 pg/ml) and protein synthesis (EC50 = 30 +/- 3.3 pg/ml). The protein kinase C (PKC) inhibitors, H-7, staurosporine, and calphostin C, reversed the rhIL-1 beta induction of TIMP-1 mRNA. PGE2 also inhibited rhIL-1 beta-stimulated TIMP-1 mRNA expression and protein secretion in a dose-dependent fashion. The concentration of PGE2 necessary to block 50% of rhIL-1 beta-stimulated TIMP-1 secretion, IC50, was 1.93 ng/ml (4.89 nM). Forskolin, and other stable derivatives of cAMP, mimicked, to a large extent, the effects of PGE2. The phorbol ester, PMA, up-regulated considerably the mRNA expression of TIMP-1 but had no effect on protein production. Calphostin C substantially reduced PMA-activated TIMP-1 expression. Staurosporine, calphostin C, H-7, and substances that elevate cellular levels of cAMP, like PGE2, also reduced basal expression and synthesis of TIMP-1. Taken together, the data suggest that PKA and C may mediate opposing effects in terms of TIMP-1 expression and secretion in human synovial fibroblasts. SN - 0730-2312 UR - https://www.unboundmedicine.com/medline/citation/7615646/Interleukin_1_beta_induction_of_tissue_inhibitor_of_metalloproteinase__TIMP_1__is_functionally_antagonized_by_prostaglandin_E2_in_human_synovial_fibroblasts_ L2 - https://doi.org/10.1002/jcb.240570406 DB - PRIME DP - Unbound Medicine ER -