TY - JOUR
T1 - Decreased salivary sulphotransferase activity correlated with inflammation and autoimmunity parameters in Sjögren'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
N1 - Funding Information:
The authors thank Dr John Schutzbach for advice and Dr Juan Carlos Aguillón for kindly donating antibodies to IFN-g and TNF-a. I.C. was supported by a fellowship granted by the Department of Post grade and Post title, Vice-Presidency of Academic Affairs, University of Chile. All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr M.-J.G. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design was by I.C., I.B., S.A. and M.-J.G. Acquisition of data by I.C., I.B., S.A, C.A., C.M., M.H., C.L., M.-J.B., M.S., V.B., S.G., U.U. and M.-J.G. Analysis and interpretation of data by I.C., I.B., U.M., S.A., U.U., A.F.G.Q., C.M. and M.-J.G.
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 - Dry mouth
KW - Gal3ST
KW - Glycosylation pathway
KW - Mucin hyposulphation
KW - Salivary glands
KW - Sjögren's syndrome
UR - http://www.scopus.com/inward/record.url?scp=84857599907&partnerID=8YFLogxK
U2 - 10.1093/rheumatology/ker351
DO - 10.1093/rheumatology/ker351
M3 - Article
C2 - 22101162
AN - SCOPUS:84857599907
SN - 1462-0324
VL - 51
SP - 482
EP - 490
JO - Rheumatology (United Kingdom)
JF - Rheumatology (United Kingdom)
IS - 3
M1 - ker351
ER -