Role of cholecystokinin-8 in nerve growth factor and nerve growth factor mRNA expression in carrageenan-induced joint inflammation in adult rats.
OBJECTIVE
The aim of our study was to investigate the role of cholecystokinin-8 (CCK-8), which is able to induce the synthesis of nerve growth factor (NGF), in the joint inflammation of carrageenan-injected rats.


METHODS
Adult rats were injected in the ankle joint with carrageenan, with or without CCK-8 or a CCK receptor antagonist (proglumide), and tissue swelling, NGF levels and NGF mRNA expression were assessed.


RESULTS
Expression of NGF and NGF mRNA increased transiently after carrageenan injection. This effect was not altered by CCK-8 injection but was inhibited by the CCK receptor antagonist. The decrease in NGF level after treatment with the antagonist was concurrent with an increase in paw swelling.


CONCLUSIONS
The results demonstrate that, whereas CCK-8 has no anti-inflammatory action in carrageenan-injected animals, proglumide induces a worsening of inflammation and reduces the expression of both NGF and NGF mRNA in inflamed ankle joints. Our data point to a regulatory action of CCK-8 on NGF synthesis during acute synovitis and suggest a role for NGF in the healing phase of inflammation.
Manni
L
L
Institute of Neurobiology and Molecular Medicine, CNR, Viale Marx 15, 00137 Rome, Italy.
Lundeberg
T
T
Tirassa
P
P
Aloe
L
L
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D002351:Carrageenan; D004195:Disease Models, Animal; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007596:Joints / Q000187:drug effects* / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D011377:Proglumide / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012844:Sincalide / Q000494:pharmacology*
D012333:RNA, Messenger; D002351:Carrageenan; D020932:Nerve Growth Factor; D011377:Proglumide; D012844:Sincalide