The protein kinase C system in focal adenitis of the lacrimal gland in the non-obese diabetic mouse model for Sjögren's syndrome.

PURPOSE: Non-obese diabetic (NOD) mice develop an autoimmune exocrinopathy characterized by hyposecretion of saliva and acinar cell atrophy. As the protein kinase C (PKC) system is involved in the signal transduction pathways associated with primary secretion and acinar cell differentiation and growth, the PKC profile was analysed in NOD mice.

METHODS

Lacrimal glands from BALB/c, NOD, NOD scid and transgenic NOD x interferon-gamma (IFN-gamma) mice were analysed for their PKC profiles using antibodies against several conventional (alpha, beta, gamma), novel (delta, epsilon, theta) and atypical (iota, lambda) PKC isoforms using the Streptavidin/HRP (horseradish peroxidase) method.

RESULTS

Acinar cells in BALB/c control mice expressed two conventional (alpha, beta) and two atypical (iota, lambda) PKC isoforms. In NOD and transgenic NOD x IFN-gamma mice the same isoforms were more strongly expressed. NOD scid mice lacked all other PKC isoforms except PKC lambda.

CONCLUSIONS

Co-expression of several PKC isoforms in single cell type may be necessary for transcriptional activation and agonist-induced secretory responses. Hyposecretion in NOD mice was paradoxically associated with up-regulation of the PKC system. This may be associated with a deranged signal transduction per se rather than with the immune-inflammation, as the transgenic NOD x IFN-gamma mice showed similar PKC profiles. The NOD model does not reproduce lack/consumption of PKC II and PKC as in Sjögren's syndrome. This may be because the receptor autoantibodies in mice are directed against the adrenergic, not muscarinic, receptors. Lack and/or low level PKC expression in NOD scid mouse may explain the excessive acinar cell apoptosis in this model.