Effects of Calorie Restriction on Transforming Growth Factor β1 and Proinflammatory Cytokines in Murine Sjogren's Syndrome

Abstract

The present study was carried out to determine whether restricting dietary calories prevents salivary gland abnormalities and modulates expression of transforming growth factor β and proinflammatory cytokines, IL-6, and TNFα in major salivary glands (SG) of autoimmune lupus-prone (NZB × NZW)F 1 (B/W) female mice. These mice develop focal lymphocytic interstitial and periductal round cell infiltrates in salivary glands similar to those of humans with Sjogren's syndrome. Weanling B/W mice were fed a nutritionally adequate semipurified diet either ad libitum (AL) or a calorie-restricted (CR; 40% less calories than AL) diet. The mice were sacrificed at 3.5 months (young) and 8.5 months (old) of age. Histopathologic and histomorphometric analyses as well as growth factor and cytokine protein and mRNA expression were carried out in the SG. Histomorphometric analysis of SG from young mice showed no differences between AL and CR mice, but old AL (vs old CR) had a 7.3-fold higher focus score and a 34-fold increase in percentage area inflammation. mRNA analysis revealed significantly higher levels of TGFβ1 in SG of old CR (6.8-fold) mice. In contrast, CR reduced mRNA expression of proinflammatory cytokines (IL-6, 2.9-fold for young and 4.8-fold for old; TNFα, old 3.9-fold). By immunoblotting, significantly higher levels of TGFβ1 protein was detected in old CR mice (vs old AL; 13.2-fold). IL-6 and TNFα proteins were undetectable in both young and old CR groups, whereas an increase in IL-6 (4.7-fold) and TNFα (9.3-fold) was observed in old AL mice. These results indicate that amelioration of the histological severity of disease in SG of B/W mice is paralleled and possibly mediated by increased expression of immunosuppressive TGFβ1 and decreased expression of proinflammatory cytokines.