Increased expression of c-jun, but not retinoic acid receptor beta, is associated with F9 teratocarcinoma stem cell differentiation induced by polyamine depletion.

alpha-Difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, and all-trans-retinoic acid (RA) are known to induce F9 teratocarcinoma stem cell differentiation. Both compounds induce the formation of the same cell type, i.e., parietal endoderm-like cells expressing tissue plasminogen activator and collagen type IV alpha-1. The present study shows that DFMO and RA induce terminal differentiation of F9 cells through different pathways. Thus, retinoic acid receptor (RAR) alpha mRNA is weakly expressed during DFMO treatment, but strongly induced during an early phase of RA treatment. RAR beta mRNA is not detectable in DFMO-treated cells, but very strongly induced by RA and maintained at a high level throughout the differentiative process. RAR gamma mRNA is relatively strongly expressed in untreated control cells and remains at approximately the same level during DFMO-induced differentiation. In RA-treated cells, however, RAR gamma mRNA is rapidly down-regulated and becomes nondetectable during the final course of differentiation. These experiments show that the differentiation of F9 cells into parietal endoderm-like cells does not necessarily involve changes in any of the RAR mRNA subtypes. Even though the steady-state levels of the RAR alpha and RAR gamma transcripts may be sufficient to support the differentiative process, our data clearly show that induction of RAR beta mRNA transcription is neither a prerequisite for F9 cell differentiation, nor an absolute consequence of the elevated c-jun mRNA expression that is consistently observed during the course of parietal endoderm differentiation.

Loss of ileal IgA+ plasma cells and of CD4+ lymphocytes in ileal Peyer's patches of vitamin A deficient rats.

Child mortality in diarrhoeal disease is increased significantly by vitamin A deficiency in poor countries. The pathological mechanisms are not known in detail. However, in this paper we report that vitamin A-deficient Wistar rats had much reduced IgA+ plasma cells in the ileal lamina propria (eightfold reduction from 470 cells/mm(2), P = 0.009), as well as a prominent reduction of CD4+ cells in the parafollicular regions of ileal Peyer's patches (reduction from 7200 to 105 cells/mm(2), P = 0.009). IL-2Ralpha-chain (CD25) positive lymphocytes in the ileal Peyer's patches were also reduced significantly in vitamin A deficiency (from 1400 to 300 cells/mm(2), P = 0.009). The density of CD8 cells tended to be increased relative to the control animals (from 5100 to 6000 cells/mm(2), not statistically significant). In conclusion, the marked decrease of lamina propria IgA+ plasma cells may be one cause of the high diarrhoeal mortality in vitamin A deficiency. This, in turn, appears to be related to reduced numbers of activated or regulatory CD4+ T cells in Peyer's patches.