Expression of pro-inflammatory TACE-TNF-α-amphiregulin axis in Sjögren's syndrome salivary glands.
The tumor-necrosis-factor-converting-enzyme (TACE)-TNF-α-Amphiregulin (AREG) axis plays an important pathogenic role in inflammatory and autoimmune disorders. However, the pathological roles of these proteins in the chronic autoimmune disease Sjögren's syndrome (SS) remain to be elucidated. It is known that the TACE-AREG axis is clearly part of a larger cascade of signals that starts with the activation of Furin, responsible for maturation of TACE that, in turn, determines the production of active TNF-α, directly involved in the up-regulation of AREG expression. This study showed that Furin, TACE, TNF-α, and AREG proteins, detected in acinar and ductal cells of human salivary glands from SS patients, increased remarkably in comparison with biopsies of labial salivary glands from healthy controls. The changes in Furin, TACE, TNF- α, and AREG proteins' level detected in salivary glands biopsies of SS patients could be responsible for pro-inflammatory cytokines overexpression characterizing Sjögren's syndrome.
Sisto
Margherita
M
Department of Human Anatomy and Histology, Laboratory of Cell Biology, University of Bari Medical School, Piazza Giulio Cesare 1, 70124 Bari, Italy. m.sisto@anatomia.uniba.it
Lisi
Sabrina
S
Lofrumento
Dario Domenico
DD
Ingravallo
Giuseppe
G
Mitolo
Vincenzo
V
D'Amore
Massimo
M
D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism; D000072198:ADAM17 Protein; D066258:Amphiregulin; D001483:Base Sequence; D015153:Blotting, Western; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary; D066255:EGF Family of Proteins; D045683:Furin / Q000235:genetics* / Q000378:metabolism; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D017421:Sequence Analysis; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
C587848:AREG protein, human; D066258:Amphiregulin; D016207:Cytokines; D018076:DNA, Complementary; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D045683:Furin; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
Nature. 1997 Feb 20;385(6618):729-33
9034190
Nature. 1997 Feb 20;385(6618):733-6
9034191
J Immunol. 1994 Jun 1;152(11):5532-9
8189070
Clin Exp Immunol. 1998 Dec;114(3):485-90
9844061
J Biol Chem. 2004 Jun 4;279(23):24179-88
15066986
J Invest Dermatol. 1998 Nov;111(5):715-21
9804327
Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):863-7
8430098
J Cell Biol. 2004 Mar 1;164(5):769-79
14993236
Ann Rheum Dis. 2003 Apr;62(4):359-62
12634239
Reumatismo. 2007 Jul-Sep;59(3):221-6
17898882
Immunol Cell Biol. 2010 Mar-Apr;88(3):297-304
19949420
Int J Immunopathol Pharmacol. 2008 Oct-Dec;21(4):1045-7
19144293
Br J Rheumatol. 1998 Jul;37(7):779-83
9714357
Ann N Y Acad Sci. 2009 Aug;1171:407-14
19723083
Apoptosis. 2006 Dec;11(12):2205-15
17051336
Autoimmunity. 2004 Jun;37(4):305-7
15518047
Int Immunol. 2009 Dec;21(12):1341-9
19854762
J Mammary Gland Biol Neoplasia. 2008 Jun;13(2):181-94
18470483
J Inflamm (Lond). 2008 Apr 27;5:5
18439312
J Lab Clin Med. 2002 Jan;139(1):13-9
11873240
Immunobiology. 2010 Nov;215(11):874-83
20061048
Semin Arthritis Rheum. 2005 Apr;34(5 Suppl1):3-6
15852247
Coll Antropol. 2004;28 Suppl 2:305-9
15571105
J Biol Chem. 2002 Apr 12;277(15):12838-45
11823465
J Biol Chem. 2001 Dec 14;276(50):46722-8
11592962
FEBS Lett. 2003 Nov 20;554(3):275-83
14623079
J Biol Chem. 1998 Jul 3;273(27):17258-68
9642297
J Reprod Dev. 2010 Jun;56(3):315-23
20168049
Clin Exp Rheumatol. 2001 Mar-Apr;19(2):131-7
11326474
Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2840-4
7708734
Mol Pharmacol. 2001 Oct;60(4):646-55
11562425
Arch Dermatol Res. 2009 Jan;301(1):87-91
18825399
DNA Res. 2005;12(6):429-39
16769699
Ann Rheum Dis. 2002 Jun;61(6):554-8
12006334
Curr Dir Autoimmun. 2010;11:1-26
20173385
Lab Invest. 1985 May;52(5):559-67
2581066
J Inflamm (Lond). 2005 Nov 25;2:15
16309552
Autoimmunity. 1992;12(3):185-91
1343766
Proc Natl Acad Sci U S A. 1988 Sep;85(17):6528-32
3413110
Arch Oral Biol. 2002 Jun;47(6):443-8
12102760
Life Sci. 2006 May 22;78(26):3051-7
16427093