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Studies on the Importance of Bombesin/GRP and Substance P in a Murine Arthritis Model
a Department of Integrative Medical Biology, Section for Anatomy, Umeå University, Umeå, Sweden b Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden c Department of Rheumatology, Umeå University Hospital, Umeå, Sweden
Key Words: arthritis • articular chondrocytes • bombesin • GRP • SP • neurokinin-1 receptor
Address for correspondence: O. Grimsholm, Department of Integrative Medical Biology, Section for Anatomy, Umeå University, SE-901 87 Umeå, Sweden. Voice: +46-90-786-51-36; fax: +46-90-786-54-80. ola.grimsholm{at}anatomy.umu.se
Interference with the effects of neuropeptides may be of potential therapeutic value for the treatment of rheumatoid arthritis (RA). Two neuropeptides that can be discussed in this context are bombesin/gastrin-releasing peptide (BN/GRP) and substance P (SP). In order to obtain new information on the possible importance of these two peptides, the patterns of immunohistochemical expression of BN/GRP and SP and their related receptors in the mouse knee joint from healthy and arthritic mice were examined. Positive staining for GRP receptor and the SP preferred receptor (the neurokinin-1 receptor [NK-1 R]) was observed in articular chondrocytes. On the whole, there was a decrease in immunoreactions for both the GRP- and the NK-1 receptors in the articular chondrocytes in joints exhibiting severe arthritis. Staining for BN/GRP and GRP receptor was seen in the inflammatory infiltrates of the arthritic joints. New evidence for the occurrence of marked effects of BN/GRP concerning both the articular chondrocytes and the inflammatory process is obtained in this study. With these findings and previous observations of neuropeptide expression patterns and functions we discuss the possibility that interventions with the effects of BN/GRP, SP, and other neuropeptides might be worthwhile in RA.
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