Sali vary and lacrimal selleck chemicals gland dysfunction in SjS is currently thought to result Inhibitors,Modulators,Libraries from a combination of pro inflammatory Inhibitors,Modulators,Libraries cytokine production capable of inducing cellular apoptosis and auto antibodies reactive with the muscarinic acetylcholine and adrenergic receptors and the action of infiltrating T cells, leading to a progressive loss of acinar cell mass. Pathological changes observed in this SjS mouse model appear to occur as a consequence of altered glandular home ostasis. Aberrant proteolytic activity, elevated apoptosis, downregulated EGF gene expression, and reduced amylase activity are commonly observed around 8 weeks of age prior to disease onset and independent of detectable autoimmunity.

While the factors driving Inhibitors,Modulators,Libraries these physiological changes remain unknown, this altered glandular homeostasis is hypothesized to be the basis for why autoreactive T cells eventually Inhibitors,Modulators,Libraries attack exocrine gland tissue. Thus, as anticipated during the development and onset of SjS, multiple genes, signaling path ways, molecular networks, and immunological processes will exhibit temporal expressions that may reflect their pathogenic functions. This concept has been strongly supported by our recent microarray studies of differentially expressed genes in the lacrimal glands during the development and onset of xerophthalmia in the NOD derived C57BL 6. NOD Aec1Aec2 mouse model of primary SjS. Taking advantage of microarray technology to screen for tem poral changes in the expression of large numbers of genes, we recently identified a set of differentially expressed genes in the salivary glands of C57BL 6.

NOD Aec1Aec2 mice at 8 versus 12 weeks of age, two time points covering the initial onset of detectable autoimmunity in this mouse model. Inhibitors,Modulators,Libraries Results of that study identified a set of sequential activations involving several biological processes and signaling pathways concep tually important in SjS disease. During the pre autoimmune phase, genes upregulated at 8 weeks of age encode factors associated with interferon, Toll like receptor, and apoptotic signaling pathways highly indicative of pro inflammatory stim uli, especially compound libraries interleukin 1 and IL 18. By 12 weeks of age, the upregulated clustered genes had switched to encode fac tors associated with adaptive immunity, especially B cell acti vation and differentiation. In the present study, we expanded this comparison of differentially expressed genes to cover the full spectrum for development and onset of SjS like disease.