The absence of 25-hydroxyvitamin D3-1α-hydroxylase potentiates the suppression of EAE in mice by ultraviolet light.
Ultraviolet B (UVB) light suppresses the development of multiple sclerosis (MS) in patients and experimental autoimmune encephalomyelitis (EAE) in mice. Although vitamin D3 is produced by ultraviolet light, the suppression of EAE by narrow band UVB (NBUVB) is independent of vitamin D3. However, it is possible that the NBUVB suppression of EAE can be further influenced by 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). We used NBUVB lamps (10KJ/m(2)) to irradiate both wild type (WT) and 1α-hydroxylase knockout mice (CYP27B1 KO) that were then induced to develop EAE. There was a complete elimination of EAE development by NBUVB in the KO mice. On the other hand, the NBUVB treatment of WT mice reduced but did not eliminate the severity or incidence of EAE. This suggests that the presence of 1,25-dihydroxyvitamin D3 actually counteracts the suppressive effect of NBUVB. In support of this concept, cytokines (IFN-γ, IL-10) and chemokine (CCL-5) mRNA in spinal cord were reduced in wild type or eliminated in the KO mice by the NBUVB. Cytokine mRNA levels in the spinal cord correlated with clinical scores in both WT and KO mice.
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, United States.
Yanping
Y
Wang
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, United States.
Steve J
SJ
Marling
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, United States.
Victoria M
VM
Martino
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, United States.
Jean M
JM
Prahl
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, United States. Electronic address: deluca@biochem.wisc.edu.
Hector F
HF
Deluca
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D002117:Calcitriol / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005260:Female; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays; D014467:Ultraviolet Therapy
C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; C556062:IL10 protein, mouse; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol
CYP27B1 knockout mice; Experimental autoimmune encephalomyelitis; Multiple sclerosis; UVB