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.