Serum transforming growth factor β1 during diabetes development in non-obese diabetic mice and humans.
Recent data show that regulatory cells with transforming growth factor (TGF)-β1-dependent activity are able to restore self-tolerance in overtly diabetic non-obese diabetic (NOD) mice. Thus, TGF-β1 seems to have a relevant role in protection from autoimmune diabetes. Our aim was to investigate the possible significance of serum TGF-β1 measurement in the natural history of diabetes in NOD mice, as well as in children positive for at least one islet-related antibody. Serum TGF-β1 (both total and active) was measured by enzyme-linked immunosorbent assay at monthly intervals in 26 NOD mice during the spontaneous development of diabetes and, on a yearly basis, in nine siblings of patients with type 1 diabetes (T1D) with a follow-up of 4 years. Diabetes appeared between the 12th week of age and the end of the study period (36 weeks) in 17 mice. TGF-β1 serum level variations occurred in the prediabetic period in both NOD mice and humans and diabetes diagnosis followed a continuing reduction of active TGF-β1 (aTGF-β1) serum levels. In mice, aTGF-β1 serum levels measured at 4 weeks of age correlated positively with severity of insulitis, and negatively with percentage of insulin-positive cells. Our findings suggest that in NOD mice serum TGF-β1 levels during the natural history of the diabetes reflect the course of islet inflammation. The measurement of aTGF-β1 in islet-related antibody-positive subjects may provide insights into the natural history of prediabetic phase of T1D.
Olivieri
A
A
Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Roma, Italy.
De Angelis
S
S
Dionisi
S
S
D'Annunzio
G
G
Locatelli
M
M
Marinaro
M
M
Bonato
V
V
Amendola
A
A
Songini
M
M
Velluzzi
F
F
Schirru
C
C
Cotichini
R
R
Stazi
M A
MA
Dotta
F
F
Lorini
R
R
Bottazzo
G F
GF
Boirivant
M
M
D000293:Adolescent; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000276:immunology / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000097:blood*
D001323:Autoantibodies; D053773:Transforming Growth Factor beta1
J Exp Med. 2005 Apr 18;201(8):1333-46
15837817
Diabetes Care. 2004 Jul;27(7):1623-9
15220238
Diabetes Metab Res Rev. 2004 Mar-Apr;20(2):137-43
15037989
Diabetes Care. 1998 Sep;21(9):1445-50
9727889
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4572-7
15070759
Immunity. 2001 Jun;14(6):715-25
11420042
Diabetologia. 2005 Aug;48(8):1565-75
15986236
Physiol Genomics. 2005 Apr 14;21(2):201-11
15671250
Diabetes Care. 2006 Jan;29 Suppl 1:S43-8
16373932
J Exp Med. 1990 Dec 1;172(6):1777-84
2258706
Annu Rev Immunol. 2005;23:447-85
15771578
J Immunol. 2002 Sep 1;169(5):2461-5
12193715
Ann Ist Super Sanita. 1999;35(2):253-63
10645659
J Immunol. 2000 Jan 1;164(1):240-7
10605017
Adv Pharmacol. 1993;24:51-76
8504067
BMJ. 2004 Mar 27;328(7442):750-4
15044291
Transplantation. 2005 May 15;79(9):1091-6
15880049
Diabetes Care. 2004 Nov;27(11):2695-700
15505007
Lancet. 1981 Dec 19-26;2(8260-61):1363-5
6118756
Diabetes. 2005 Jan;54(1):92-9
15616015
J Exp Med. 2005 Apr 4;201(7):1061-7
15809351
Nat Rev Immunol. 2007 Dec;7(12):988-94
17982429
Nat Med. 2003 Sep;9(9):1202-8
12937416