Decreased salivary sulphotransferase activity correlated with inflammation and autoimmunity parameters in Sjogren's syndrome patients

TY - JOUR

T1 - Decreased salivary sulphotransferase activity correlated with inflammation and autoimmunity parameters in Sjogren's syndrome patients

AU - Castro, Isabel

AU - Aguilera, Sergio

AU - Brockhausen, Inka

AU - Alliende, Cecilia

AU - Quest, Andrew F G

AU - Molina, Claudio

AU - Urzúa, Ulises

AU - Mandel, Ulla

AU - Bahamondes, Verónica

AU - Barrera, María-José

AU - Sánchez, Marianela

AU - González, Sergio

AU - Hermoso, Marcela

AU - Leyton, Cecilia

AU - González, María-Julieta

PY - 2012/3

Y1 - 2012/3

N2 - Objectives: To determine the expression and enzymatic activities of sulphotransferases involved in mucin hyposulphation in labial salivary glands (LSGs) from SS patients and to correlate sulphotransferase activity with clinical parameters such as secretion, inflammation and serology. Methods: LSG from 31 SS patients and 31 control subjects were studied. Relative mRNA and protein levels of Gal3-O-sulphotransferases (Gal3STs) and β1,3-galactosyltransferase-5 (β3GalT5) were determined by quantitative RT-PCR and western blotting, respectively. Enzymatic activities were quantified using radioactively labelled donor substrates and specific acceptor substrates. Products were purified by chromatography. Spearman's correlation analysis was used to compare data. Results: The levels of Gal3ST activity were significantly decreased in SS patients, without changes in mRNA and protein levels, while the enzymatic activities of glycosyltransferases involved in mucin glycosylation were similar in both groups. An inverse correlation was observed between Gal3ST activity and glandular function measured by scintigraphy, but not with unstimulated salivary flow. Gal3ST activity was inversely correlated with focus score, TNF-α levels and presence of the autoantibodies Ro/SS-A and La/SS-B. Conclusion: The decrease in sulphotransferase activity provides an explanation for mucin hyposulphation observed in the LSGs from SS patients. The decrease in Gal3STs activity was not a consequence of reduced gene expression, but probably due to alterations in the enzyme activity regulation. Interestingly, the levels of sulphotransferase activity detected correlated well with secretory function, inflammation and serology. Finally, we postulate that pro-inflammatory cytokines induced by autoantibodies, such as Ro/SS-A and La/SS-B in SS patients, may modulate Gal3ST activity, thereby altering mucin quality and leading to mouth dryness.

AB - Objectives: To determine the expression and enzymatic activities of sulphotransferases involved in mucin hyposulphation in labial salivary glands (LSGs) from SS patients and to correlate sulphotransferase activity with clinical parameters such as secretion, inflammation and serology. Methods: LSG from 31 SS patients and 31 control subjects were studied. Relative mRNA and protein levels of Gal3-O-sulphotransferases (Gal3STs) and β1,3-galactosyltransferase-5 (β3GalT5) were determined by quantitative RT-PCR and western blotting, respectively. Enzymatic activities were quantified using radioactively labelled donor substrates and specific acceptor substrates. Products were purified by chromatography. Spearman's correlation analysis was used to compare data. Results: The levels of Gal3ST activity were significantly decreased in SS patients, without changes in mRNA and protein levels, while the enzymatic activities of glycosyltransferases involved in mucin glycosylation were similar in both groups. An inverse correlation was observed between Gal3ST activity and glandular function measured by scintigraphy, but not with unstimulated salivary flow. Gal3ST activity was inversely correlated with focus score, TNF-α levels and presence of the autoantibodies Ro/SS-A and La/SS-B. Conclusion: The decrease in sulphotransferase activity provides an explanation for mucin hyposulphation observed in the LSGs from SS patients. The decrease in Gal3STs activity was not a consequence of reduced gene expression, but probably due to alterations in the enzyme activity regulation. Interestingly, the levels of sulphotransferase activity detected correlated well with secretory function, inflammation and serology. Finally, we postulate that pro-inflammatory cytokines induced by autoantibodies, such as Ro/SS-A and La/SS-B in SS patients, may modulate Gal3ST activity, thereby altering mucin quality and leading to mouth dryness.

KW - Adult

KW - Aged

KW - Autoimmunity

KW - Blotting, Western

KW - Case-Control Studies

KW - DNA Primers

KW - Female

KW - Galactosyltransferases

KW - Glycosylation

KW - Humans

KW - Immunohistochemistry

KW - Inflammation

KW - Male

KW - Middle Aged

KW - Mucin-5B

KW - RNA, Messenger

KW - Real-Time Polymerase Chain Reaction

KW - Salivary Glands, Minor

KW - Sjogren's Syndrome

KW - Sulfurtransferases

KW - Young Adult

U2 - 10.1093/rheumatology/ker351

DO - 10.1093/rheumatology/ker351

M3 - Journal article

C2 - 22101162

SN - 1462-0324

VL - 51

SP - 482

EP - 490

JO - Rheumatology

JF - Rheumatology

IS - 3

ER -