Androgens and Integrins in Salivary Glands in Sjogren's Syndrome

Objective. Laminin alpha 1-chain normally induces intercalated duct progenitors to differentiate to acinar cells through integrin (INT) alpha 1 beta 1 and alpha 2 beta 1 receptors. Maintenance of acinar cells is impaired in Sjogren's syndrome (SS), which is also characterized by low levels of serum and salivary androgens. We hypothesized that androgens normally support salivary gland remodeling by upregulating either laminin at chain or its cellular alpha 1 or alpha 2 INT subunit-containing receptors. Methods. Intercalated duct and acinar human salivary gland (HSG) cells and labial salivary gland (LSG) biopsies from healthy controls and patients with SS were cultured without or with sex steroids. Laminin alpha 1 chain and INT alpha 1 and alpha 2 subunits were studied using quantitative reverse-transcription real-time polymerase chain reaction and INT alpha 1 and alpha 2 subunits using immunofluorescence staining. Results. TNT alpha 1-subunit and alpha 2-subunit messenger RNA (mRNA) levels were increased in intercalated duct and acinar cells by DHEA and testosterone. In contrast, laminin alpha 1-chain mRNA levels were not affected. The upregulating effect of DHEA on INT subunits was also seen at the protein level. DHEA also increased mRNA levels of both INT subunits in healthy but not SS LSG. Conclusion. Androgens increased INT at and alpha 2 subunits in tubuloepithelial cells and in healthy LSG, but in SS salivary glands this androgen regulation was defective, which is likely to contribute to defective outside-in signaling, acinar atrophy, and ductal cell hyperplasia. (First Release May 1 2010; J Rheumatol 2010;37:1181-7; doi:10.3899/jrheum.091354)