Plasma fetuin-A/α2-HS-glycoprotein correlates negatively with inflammatory cytokines, chemokines and activation biomarkers in individuals with type-2 diabetes.
BACKGROUND
Fetuin-A/AHSH is a novel hepatokine that acts as a vascular calcification inhibitor and as an endogenous TLR-4 ligand. Fetuin-A may act as a positive or negative acute phase protein (APP) in disease conditions. The relationship between circulatory fetuin-A and inflammatory biomarkers in type-2 diabetes (T2D) remains controversial. Therefore, the purpose of this study was to determine the plasma fetuin-A levels in 53 T2D (BMI = 29.7 ± 4.5 kg/m2) and 72 non-diabetic individuals (BMI = 28.2 ± 5.8 kg/m2) using premixed 38-plex MAP human cytokine/chemokine magnetic bead immunoassays and the data (mean ± SEM) were statistically analyzed to determine Pearson's correlation (r) between fetuin-A and detected analytes; P-values ≤0.05 were considered significant.


RESULTS
The data show that plasma fetuin-A levels were comparable in both groups (P = 0.27) and in T2D individuals, fetuin-A associated negatively (P ≤ 0.05) with a large number of proinflammatory cytokines/chemokines and activation biomarkers including TNF-α, IFN-α2, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-3, IL-4, IL-7, IL-9, IL-12p40/p70, IL-15, CCL-2, CCL-4, CCL-11, CCL-22, CXCL-8, CX3CL-1, EFF-2, EGF, G-CSF, GM-CSF, GRO, sCD40L, and VEGF. In non-diabetics, fetuin-A also correlated positively with certain TH2 cytokines (IL-5, IL-13) and chemokines (CCL-3, CCL-5, CCL-7). Notably, in vitro fetuin-A production was significantly suppressed in HepG2 cells treated with TNF-α, IL-1β, and IFN-γ which supported the clinical findings of a negative association between fetuin A and inflammatory mediators.


CONCLUSIONS
The negative association between circulatory fetuin-A and systemic inflammatory mediators in T2D patients suggests that plasma fetuin-A may have predictive significance as a negative APP in metabolic disease.
Immunology & Innovative Cell Therapy Unit, Dasman Diabetes Institute (DDI), P.O. Box 1180, Dasman, 15462, Kuwait. sardar.sindhu@dasmaninstitute.org.
Sardar
S
Sindhu
Immunology & Innovative Cell Therapy Unit, Dasman Diabetes Institute (DDI), P.O. Box 1180, Dasman, 15462, Kuwait.
Nadeem
N
Akhter
Immunology & Innovative Cell Therapy Unit, Dasman Diabetes Institute (DDI), P.O. Box 1180, Dasman, 15462, Kuwait.
Steve
S
Shenouda
Immunology & Innovative Cell Therapy Unit, Dasman Diabetes Institute (DDI), P.O. Box 1180, Dasman, 15462, Kuwait.
Ajit
A
Wilson
Immunology & Innovative Cell Therapy Unit, Dasman Diabetes Institute (DDI), P.O. Box 1180, Dasman, 15462, Kuwait. rasheed.ahmad@dasmaninstitute.org.
Rasheed
R
Ahmad
Chemokines; Fetuin-A; Metabolic inflammation; Proinflammatory cytokines; Type-2 diabetes; α2-HS-glycoprotein
Eur J Gastroenterol Hepatol. 2000 Jul;12(7):761-6
10929903
Diabetes. 2008 Oct;57(10):2762-7
18633113
PLoS One. 2011 Feb 08;6(2):e16945
21347455
J Mol Med (Berl). 2002 Nov;80(11):696-702
12436346
Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14429-34
9826717
Regul Pept. 2012 Oct 10;178(1-3):6-10
22387701
Arthritis Res Ther. 2006;8 Suppl 2:S2
16899106
Clinics (Sao Paulo). 2011;66(5):911-2
21789399
Diabetes Metab Syndr. 2015 Oct-Dec;9(4):258-65
25450818
Eur J Clin Invest. 2008 Nov;38(11):804-11
19021697
Clin Lab. 2010;56(5-6):191-5
20575466
Exp Ther Med. 2015 May;9(5):1921-1930
26136915
Diabetes Care. 2010 Feb;33(2):408-10
19910501
Circulation. 2008 Dec 9;118(24):2555-62
19029462
Endocr Pract. 2014 Dec;20(12 ):1345-51
25370330
Iran J Kidney Dis. 2013 Nov;7(6):440-5
24241089
Curr Mol Med. 2012 Jun;12(5):625-33
22292896
Diabetes Care. 2011 Jan;34(1):156-61
20929991
Atherosclerosis. 2010 Jan;208(1):290-6
19709661
Int J Obes (Lond). 2015 May;39(5):734-41
25468829
Recent Pat Endocr Metab Immune Drug Discov. 2011 May;5(2):124-46
22074587
J Comp Neurol. 2000 Jul 31;423(3):373-88
10870079
Intern Med. 2007;46(20):1685-91
17938521