Secretion of Gelatinases and Activation of Gelatinase A (MMP-2) by Human Rheumatoid Synovial Fibroblasts

2001 ◽  
Vol 382 (10) ◽  
pp. 1491-1499 ◽  
Author(s):  
H. Smolian ◽  
A. Aurer ◽  
M. Sittinger ◽  
J. Zacher ◽  
J.-P. Bernimoulin ◽  
...  
Keyword(s):  
Map Kinase ◽  
Cell Line ◽  
Protein Kinases ◽  
Kinase Inhibitors ◽  
Human Fibroblasts ◽  
Specific Inhibitor ◽  
Fibroblast Cell ◽  
Synovial Fibroblasts ◽  
P38 Map Kinase ◽  
Gelatinase A

Abstract In monolayer cultures human rheumatoid synovial fibroblasts (HRSF) secrete gelatinase A (MMP-2) and, unlike other human fibroblasts, to a minor extent also gelatinase B (MMP-9) as inactive proenzymes. In this regard HRSF resemble the fibrosarcoma cell line HT-1080. Unlike HT-1080, however, HRSF do not increase the secretion of MMP-9 in response to phorbol-12-myristate-13-acetate. This indicates that in HRSF the protein kinase C pathway for an enhanced MMP-9 secretion is inactive. None of the substances used in our study increased MMP-9 secretion, but some of them inhibited MMP-9 secretion. The secretion of MMP-2 could not be enhanced either, not even by dbcAMP, which has been reported to be effective in Sertoli and peritubular cells. Activation of MMP-2 in HRSF could be induced by treatment with concanavalin A (ConA) or cytochalasin D, as was shown for other cell types. This activation was not accompanied by a significant change in the amount of secreted TIMP-1 and TIMP-2. In contrast to reports on human skin fibroblasts, however, the activation of MMP-2 could not be induced in HRSF by treatment of the cells with monensin or sodium orthovanadate. Moreover, monensin was shown to act as an inhibitor of ConA or cytochalasin Dmediated activation. Additionally, and in contrast to a report on a rat fibroblast cell line, MMP-2 activation is not mediated via the MAP kinase pathway in HRSF: PD 98059, a specific inhibitor of MAP kinase kinase, did not inhibit the activation of MMP-2. Similarly ineffective were PD 169316, an inhibitor for p38 MAP kinase, other inhibitors for protein kinases as lavendustin A, Gö 6983, wortmannin, rapamycin, as well as the protein tyrosine kinase inhibitors herbimycin A and genistein. Only staurosporin, a broad spectrum inhibitor of protein kinases, and the ionophores monensin and A 23187 effectively inhibited MMP-2 activation in HRSF. Our results demonstrate that MMP-2 can be activated by quite different pathways, and that different cells, even when belonging to the fibroblast family, do not necessarily use the same activating pathways.

scholarly journals Differential effects of p38 MAP kinase inhibitors SB203580 and SB202190 on growth and migration of human MDA-MB-231 cancer cell line

2017 ◽  
Vol 69 (4) ◽  
pp. 711-724 ◽  
Author(s):  
Şükrü Aydın Düzgün ◽  
Azmi Yerlikaya ◽  
Sezgin Zeren ◽  
Zülfü Bayhan ◽  
Emrah Okur ◽  
...  
Keyword(s):  
Map Kinase ◽  
Cell Line ◽  
Cancer Cell ◽  
Kinase Inhibitors ◽  
Cancer Cell Line ◽  
P38 Map Kinase ◽  
Differential Effects ◽  
And Migration ◽  
P38 Map Kinase Inhibitors

Roscovitine, a specific inhibitor of cyclin-dependent protein kinases, reversibly inhibits chromatin condensation during in vitro maturation of porcine oocytes

Zygote ◽  
2001 ◽  
Vol 9 (4) ◽  
pp. 309-316 ◽  
Author(s):  
Carsten Krischek ◽  
Burkhard Meinecke
Keyword(s):  
Map Kinase ◽  
Protein Kinases ◽  
Chromatin Condensation ◽  
Specific Inhibitor ◽  
Histone H1 ◽  
Dependent Manner ◽  
Free Medium ◽  
Concentration Dependent Manner ◽  
Dependent Protein

In the present study the effects of roscovitine on the in vitro nuclear maturation of porcine oocytes were investigated. Roscovitine, a specific inhibitor of cyclin-dependent protein kinases, prevented chromatin condensation in a concentration-dependent manner. This inhibition was reversible and was accompanied by non-activation of p34cdc2/histone H1 kinase. It also decreased enzyme activity of MAP kinase, suggesting a correlation between histone H1 kinase activation and the onset of chromatin condensation. The addition of roscovitine (50 μM) to extracts of metaphase II oocytes revealed that the MAP kinase activity was not directly affected by roscovitine, which indicates a possible link between histone H1 and MAP kinase. Chromatin condensation occurred between 20 and 28 h of culture of cumulus-oocyte complexes (COCs) in inhibitor-free medium (germinal vesicle stage I, GV1: 74.6% and 13.7%, respectively). Nearly the same proportion of chromatin condensation was detected in COCs incubated initially in inhibitor-free medium for 20-28 h and subsequently in roscovitine-supplemented medium (50 μM) for a further 2-10 h (GV I: 76.2% and 18.8%, respectively). This observation indicates that roscovitine prevents chromatin condensation even after an initial inhibitor-free cultivation for 20 h. Extending this initial incubation period to ≥22 h led to an activation of histone H1 and MAP kinase and increasing proportions of oocytes exhibiting chromatin condensation in the presence of roscovitine. It is concluded that histone H1 kinase is involved in the induction of chromatin condensation during in vitro maturation of porcine oocytes.

Functional Role of p38 Mitogen Activated Protein Kinase in Platelet Activation induced by a Thromboxane A2 Analogue and by 8-iso-prostaglandin F2 α

2002 ◽  
Vol 87 (05) ◽  
pp. 888-898 ◽  
Author(s):  
Stefania Gaino ◽  
Valeria Zuliani ◽  
Rosa Tommasoli ◽  
Donatella Benati ◽  
Riccardo Ortolani ◽  
...  
Keyword(s):  
Map Kinase ◽  
Platelet Activation ◽  
Tyrosine Kinases ◽  
Actin Polymerization ◽  
Shape Change ◽  
Specific Inhibitor ◽  
P38 Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Kinase Phosphorylation

SummaryWe investigated similarities in the signaling pathways elicited by the F2 isoprostane 8-iso-PGF2α and by low doses of U46619 to induce platelet activation. Both 0.01-0.1 µmol/L U46619 and 0.01-1 µmol/L 8-isoPGF2α triggered shape change and filopodia extension, as well as adhesion to immobilized fibrinogen of washed platelets. At these doses the two platelet agonists failed to trigger secretion and aggregation, which were however induced by higher doses of U46619 (0.1-1 µmol/L). SB203580 (1-10 µmol/L), a specific inhibitor of the p38 mitogen activated protein (MAP) kinase blunted platelet shape change and adhesion induced by 0.05-1 µmol/L 8-iso-PGF2α and by 0.01 µmol/L U46619. These platelet responses were also inhibited by 20 µmol/L cytochalasin D, an inhibitor of actin polymerization, and 50 µmol/L piceatannol, an inhibitor of the Syk tyrosine kinases. Both 8-iso-PGF2α and U46619-induced p38 MAP kinase phosphorylation in suspended platelets and this was inhibited by piceatannol, indicating that Syk activation occurs upstream p38 MAP kinase phosphorylation. These findings suggest that the signaling pathway triggered by both 8-iso-PGF2α and low concentrations of U46619 to induce platelet adhesion and shape change implicates Syk, the p38 MAP kinase, and actin polymerization.

scholarly journals Inhibition of Wnt/β-Catenin Signaling by p38 MAP Kinase Inhibitors Is Explained by Cross-Reactivity with Casein Kinase Iδ/ɛ

2011 ◽  
Vol 18 (4) ◽  
pp. 485-494 ◽  
Author(s):  
Folkert Verkaar ◽  
Antoon A. van der Doelen ◽  
Jos F.M. Smits ◽  
W. Matthijs Blankesteijn ◽  
Guido J.R. Zaman
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitors ◽  
Cross Reactivity ◽  
P38 Map Kinase ◽  
Casein Kinase ◽  
P38 Map Kinase Inhibitors

scholarly journals Differential role of cAMP, cGMP and Ca2+ and involvement of kinases and CBP-CREB-CRE pathway in regulation of arylalkylamine N-acetyltransferase 2 gene in the pineal organ of air-breathing catfish, Clarias gariepinus

2021 ◽  
Author(s):  
Hijam Nonibala ◽  
Braj Bansh Prasad Gupta
Keyword(s):  
Gene Expression ◽  
Map Kinase ◽  
Gene Transcription ◽  
Pineal Organ ◽  
Clarias Gariepinus ◽  
Specific Inhibitor ◽  
P38 Map Kinase ◽  
Camp And Cgmp

Abstract Transcription of arylalkylamine N-acetyltransferase 2 (aanat2) gene leads to formation of AANAT2 - the rate-limiting enzyme in melatonin synthesis pathway in photosensitive fish pineal organ. However, unlike in avian and mammalian pineal gland, there is practically no information on signal transduction pathway(s) involved in regulation of aanat2 gene transcription in the fish pineal organ. Therefore, we investigated the role of important molecular components of signalling via cAMP, cGMP, Ca2+ involving PKA, PKG, PKC, MeK and p38 MAP kinase as well as possible role of serine/threonine phosphatases, CREB and CBP using their specific inhibitors and/or activators in aanat2 gene transcription in the fish pineal organ maintained under in vitro culture-conditions. db-cAMP and db-cGMP stimulated the expression of aanat2 gene. db-cAMP- and cGMP-induced aanat2 gene expression was significantly reduced in the presence of H-89 (specific inhibitor of PKA), KT5823 (specific inhibitor of PKG), chelerythrine chloride (specific inhibitor of PKC), U0126 ethanolate (specific inhibitor of MeK) and SB 202190 monohydrochloride hydrate (specific inhibitor of p38 MAP kinase). Inhibitors of PP1 and PP2A significantly increased aanat2 gene expression as well as significantly reduced cAMP- and cGMP-induced gene transcription, while inhibitor of PP2B had no effect on aanat2 gene expression. Inhibitors of both CREB and CBP-CREB interaction completely blocked cAMP-induced aanat2 gene transcription. Based on these findings, we suggest that cAMP, cGMP and Ca2+ stimulate aanat2 gene transcription via PKA, PKG and PKC, respectively. Further, protein phosphatases and CBP-CREB-CRE pathway are actively involved in regulation of on aanat2 gene expression in the fish pineal organ.

p38 MAP kinase inhibitors. Part 3: SAR on 3,4-dihydropyrimido[4,5-d]pyrimidin-2-ones and 3,4-dihydropyrido[4,3-d]pyrimidin-2-ones

2006 ◽  
Vol 16 (16) ◽  
pp. 4400-4404 ◽  
Author(s):  
Swaminathan R. Natarajan ◽  
David D. Wisnoski ◽  
James E. Thompson ◽  
Edward A. O’Neill ◽  
Stephen J. O’Keefe
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitors ◽  
P38 Map Kinase ◽  
P38 Map Kinase Inhibitors

Metabolically Stable Dibenzo[b,e]oxepin-11(6H)-ones as Highly Selective p38 MAP Kinase Inhibitors: Optimizing Anti-Cytokine Activity in Human Whole Blood

2013 ◽  
Vol 56 (21) ◽  
pp. 8561-8578 ◽  
Author(s):  
Benjamin Baur ◽  
Kirsten Storch ◽  
Kathrin E. Martz ◽  
Marcia I. Goettert ◽  
André Richters ◽  
...  
Keyword(s):  
Map Kinase ◽  
Whole Blood ◽  
Kinase Inhibitors ◽  
P38 Map Kinase ◽  
Human Whole Blood ◽  
P38 Map Kinase Inhibitors

scholarly journals Legionella pneumophila Suppresses Macrophage Interleukin-12 Production by Activating the p42/44 Mitogen-Activated Protein Kinase Cascade

2003 ◽  
Vol 71 (11) ◽  
pp. 6672-6675 ◽  
Author(s):  
Kazuto Matsunaga ◽  
Hiroyuki Yamaguchi ◽  
Thomas W. Klein ◽  
Herman Friedman ◽  
Yoshimasa Yamamoto
Keyword(s):  
Map Kinase ◽  
Legionella Pneumophila ◽  
Kinase Inhibitors ◽  
Selective Inhibition ◽  
P38 Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Interleukin 12 ◽  
Map Kinase Cascade ◽  
Mitogen Activated Protein ◽  
Kinase Cascade

ABSTRACT A possible involvement of the mitogen-activated protein (MAP) kinase cascade in the inhibition of macrophage interleukin-12 (IL-12) production by Legionella pneumophila infection was examined. The results of MAP kinase inhibition by p42/44 and p38 MAP kinase inhibitors and of p42/44 MAP kinase activity assays indicate that L. pneumophila infection of macrophages causes a selective inhibition of lipopolysaccharide-induced IL-12 production by activating the p42/44 MAP kinase cascade. In addition, it was also revealed that the p38 MAP kinase may be important for the production of IL-12 but not for the inhibition caused by L. pneumophila infection.

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