| Abstract: |
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.Lacrimal glands from BALB/c, NOD, NOD scid and transgenic NOD × interferon-γ (IFN-γ) mice were analysed for their PKC profiles using antibodies against several conventional (α, β, γ), novel (δ, ε, θ) and atypical (ι, λ) PKC isoforms using the Streptavidin/HRP (horseradish peroxidase) method.Acinar cells in BALB/c control mice expressed two conventional (α, β) and two atypical (ι, λ) PKC isoforms. In NOD and transgenic NOD × IFN-γ mice the same isoforms were more strongly expressed. NOD scid mice lacked all other PKC isoforms except PKC λ.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 × IFN-γ 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. |
