Beta-endorphin regulation of MAPKs in cultured human articular chondrocytes: MAPK inhibitors prevent the increase of IL-1 beta protein levels during beta-endorphin stimulation.
We investigated the effect of beta-endorphin on the activities of mitogen-activated protein kinases in cultured human articular chondrocytes in order to elucidate its effect on cartilage. Monolayer cultures of chondrocytes obtained from patients undergoing total knee arthroplasty were treated with 60, 600, or 6000 ng/ml beta-endorphin, or 100 ng/ml naltrexone combined with 600 ng/ml beta-endorphin. The regulation of three major mitogen-activated protein kinases phosphorylation, ERKp44/p42, p38, and JNK, was determined by Western blotting. We also examined the influence of specific mitogen-activated protein kinase inhibitors on IL-1 beta protein levels during beta-endorphin stimulation. The results demonstrate that beta-endorphin, dependent on concentration and duration of stimulation, significantly affected the activation of the three mitogen-activated protein kinases in cultured human articular chondrocytes. Naltrexone in some cases significantly regulated the mitogen-activated protein kinases in different ways when added to beta-endorphin 600 ng/ml. Furthermore, specific mitogen-activated protein kinase inhibitors hindered the increase of IL-1 beta during beta-endorphin incubation. The effect of beta-endorphin seen in this study is considered critical for the production of several mediators of cartilage damage in an arthritic joint.
Andjelkov
Nenad
N
Department of Orthopaedics, University of Tromsoe, Norway. nenad.andjelkov@fagmed.uit.no
Elvenes
Jan
J
Knutsen
Gunnar
G
Johansen
Oddmund
O
D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D013997:Time Factors; D001615:beta-Endorphin / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D053583:Interleukin-1beta; D047428:Protein Kinase Inhibitors; D001615:beta-Endorphin; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases