Bone marrow-derived macrophages express functional CGRP receptors and respond to CGRP by increasing transcription of c-fos and IL-6 mRNA.
Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide with inflammatory and immunoregulatory properties. CGRP inhibits IL-7 responses by B cell precursors by direct and indirect mechanisms. We recently found that CGRP induces IL-6 and TNF-alpha in long-term bone marrow cultures and that IL-6 and TNF-alpha also inhibit IL-7 responses. Because these are heterogeneous cultures, it was not clear which cells produced IL-6 and TNF-alpha. To determine whether bone marrow-derived macrophages (BMDM) were the source, we did studies to determine whether BMDMs express mRNAs for CGRP receptors and whether CGRP induces c-fos, IL-6, and TNF-alpha mRNA. We found that BMDMs express mRNAs for CRLR and RAMP1, the minimal components for CGRP receptors. CGRP also stimulated dose- and time-dependent increases in c-fos and IL-6. In contrast, CGRP did not induce TNF-alpha in BMDMs. These results suggest that BMDMs are a source of CGRP-induced IL-6 in bone marrow.
Fernandez
S
S
Department of Microbiology and Immunology, University of Kentucky College of Medicine, Lexington, Kentucky, 40536, USA.
Knopf
M A
MA
Bjork
S K
SK
McGillis
J P
JP
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D058262:Receptor Activity-Modifying Protein 1; D058261:Receptor Activity-Modifying Proteins; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016760:Proto-Oncogene Proteins c-fos; C545505:Ramp1 protein, mouse; D058262:Receptor Activity-Modifying Protein 1; D058261:Receptor Activity-Modifying Proteins; D018015:Receptors, Calcitonin Gene-Related Peptide; D015740:Calcitonin Gene-Related Peptide