Potentiation of IL-1-induced BALB/3T3 fibroblast proliferation by neuropeptides.
The interactions between IL-1 and several neuropeptides associated with pain and inflammation were examined in the context of fibroblast proliferation as a paradigm for the synovial hyperplasia associated with chronic rheumatoid arthritis. The BALB/3T3 fibroblast cell line, which proliferates in response to increasing doses of IL-1, demonstrated enhanced proliferation after a 72-h culture period when various neuropeptides were included with IL-1 in serum-free medium. Thus, bradykinin, at concentrations between 10(-8) and 10(-5) M, moderately promoted [3H]TdR incorporation in vitro in the BALB/3T3 cells, and substance P at approximately 3 x 10(-9) to 3 x 10(-7) M demonstrated minor proliferative activity. However, when the cells were cultured with IL-1 plus substance P or IL-1 plus BK, the ensuing proliferative responses, as measured by [3H]TdR incorporation, were consistently magnified greater than or equal to twofold above the anticipated additive response caused by IL-1 in combination with either of those neuropeptides. Combinations of IL-1 and SP, or IL-1 and BK, also provoked increases in cell numbers that did not occur when the mediators were tested individually. In other experiments, we tested neurokinin-A, Neurokinin-B, histamine, and serotonin. These results are discussed with respect to neurogenic contributions to the immunopathology of IL-1-mediated inflammation.
Kimball
E S
ES
Department of Biological Research, Janssen Research Foundation, Spring House, PA 19477.
Fisher
M C
MC
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D007375:Interleukin-1; D051379:Mice; D008807:Mice, Inbred BALB C; D009479:Neuropeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D009479:Neuropeptides; D010446:Peptide Fragments; D012701:Serotonin; D013373:Substance P; D006632:Histamine; D001920:Bradykinin