The calcitonin/calcitonin gene related peptide-alpha gene is not required for 1alpha,25-dihydroxyvitamin D3-mediated suppression of experimental autoimmune encephalomyelitis.
The active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), can suppress disease in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Calcium appears to be a critical component of 1,25(OH)(2)D(3)-mediated suppression of EAE, as complete disease prevention only occurs with a concomitant increase in serum calcium levels. Calcitonin (CT) is a peptide hormone released in response to acute increases in serum calcium, which led us to explore its importance in 1,25(OH)(2)D(3)-mediated suppression of EAE. Previously, we discovered that co-administration of pharmacological doses of CT enhanced the suppressive effect of 1,25(OH)(2)D(3) on EAE, suggesting CT may play a role in 1,25(OH)(2)D(3)-mediated suppression of EAE. To determine the importance of CT in EAE we have utilized a mouse strain in which the gene encoding CT and its alternative splice product, calcitonin gene related peptide-alpha (CGRP), have been deleted. Deletion of the CT/CGRP gene had no effect on EAE progression. Furthermore, treatment with 1,25(OH)(2)D(3) suppressed EAE in CT/CGRP knock-out mice equal to that in wild type mice. Therefore, we conclude that CT is not necessary for 1,25(OH)(2)D(3)-mediated suppression of EAE.
Becklund
Bryan R
BR
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
James
Bradley J
BJ
Gagel
Robert F
RF
DeLuca
Hector F
HF
D000818:Animals; D002116:Calcitonin / Q000494:pharmacology* / Q000627:therapeutic use; D002118:Calcium / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000517:prevention & control; D005260:Female; D006934:Hypercalcemia; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D002116:Calcitonin; D002118:Calcium