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

Isabel Castro; Sergio Aguilera; Inka Brockhausen; Cecilia Alliende; Andrew F.G. Quest; Claudio Molina; Ulises Urzúa; Ulla Mandel; Verónica Bahamondes; María José Barrera; Marianela Sánchez; Sergio González; Marcela Hermoso; Cecilia Leyton; María Julieta González

doi:10.1093/rheumatology/ker351

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

Isabel Castro, Sergio Aguilera, Inka Brockhausen, Cecilia Alliende, Andrew F.G. Quest, Claudio Molina, Ulises Urzúa, Ulla Mandel, Verónica Bahamondes, María José Barrera, Marianela Sánchez, Sergio González, Marcela Hermoso, Cecilia Leyton, María Julieta González^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

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.

Original language	English
Article number	ker351
Pages (from-to)	482-490
Number of pages	9
Journal	Rheumatology (United Kingdom)
Volume	51
Issue number	3
DOIs	https://doi.org/10.1093/rheumatology/ker351
State	Published - 2012
Externally published	Yes

Bibliographical note

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.

ASJC Scopus subject areas

Rheumatology
Pharmacology (medical)

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10.1093/rheumatology/ker351

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Castro, I., Aguilera, S., Brockhausen, I., Alliende, C., Quest, A. F. G., Molina, C., Urzúa, U., Mandel, U., Bahamondes, V., Barrera, M. J., Sánchez, M., González, S., Hermoso, M., Leyton, C., & González, M. J. (2012). Decreased salivary sulphotransferase activity correlated with inflammation and autoimmunity parameters in Sjögren's syndrome patients. Rheumatology (United Kingdom), 51(3), 482-490. Article ker351. https://doi.org/10.1093/rheumatology/ker351

@article{c3e2098676ca44878227f924258b7493,

title = "Decreased salivary sulphotransferase activity correlated with inflammation and autoimmunity parameters in Sj{\"o}gren's syndrome patients",

abstract = "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.",

keywords = "Dry mouth, Gal3ST, Glycosylation pathway, Mucin hyposulphation, Salivary glands, Sj{\"o}gren's syndrome",

author = "Isabel Castro and Sergio Aguilera and Inka Brockhausen and Cecilia Alliende and Quest, {Andrew F.G.} and Claudio Molina and Ulises Urz{\'u}a and Ulla Mandel and Ver{\'o}nica Bahamondes and Barrera, {Mar{\'i}a Jos{\'e}} and Marianela S{\'a}nchez and Sergio Gonz{\'a}lez and Marcela Hermoso and Cecilia Leyton and Gonz{\'a}lez, {Mar{\'i}a Julieta}",

note = "Funding Information: The authors thank Dr John Schutzbach for advice and Dr Juan Carlos Aguill{\'o}n 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.",

year = "2012",

month = mar,

doi = "10.1093/rheumatology/ker351",

language = "English",

volume = "51",

pages = "482--490",

journal = "Rheumatology (United Kingdom)",

issn = "1462-0324",

publisher = "Oxford University Press",

number = "3",

}

Castro, I, Aguilera, S, Brockhausen, I, Alliende, C, Quest, AFG, Molina, C, Urzúa, U, Mandel, U, Bahamondes, V, Barrera, MJ, Sánchez, M, González, S, Hermoso, M, Leyton, C & González, MJ 2012, 'Decreased salivary sulphotransferase activity correlated with inflammation and autoimmunity parameters in Sjögren's syndrome patients', Rheumatology (United Kingdom), vol. 51, no. 3, ker351, pp. 482-490. https://doi.org/10.1093/rheumatology/ker351

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 -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

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