PREPROSOMATOSTATIN MESSENGER-RNA IS EXPRESSED BY INFLAMMATORY CELLS AND INDUCED BY INFLAMMATORY MEDIATORS AND CYTOKINES

Somatostatin (SOM) is a 14-amino acid cyclic peptide that regulates gr anulomatous inflammation, SOM inhibits the release of IFN-gamma from m urine granuloma T cells that express SOM receptors, SOM is synthesized as preprosomatostatin (ppSOM), a precursor peptide that is cleaved to release active SOM. In this paper, we demonstrate that granuloma cell s express mRNA for this important immunoregulator, and that inflammato ry mediators rapidly induce ppSOM mRNA in the splenocytes of uninfecte d, normal (NL) mice, We developed a sensitive, quantitative PCR assay that measures ppSOM mRNA down to 100 transcripts per mu g of total RNA , Dispersed granuloma cells expressed authentic ppSOM mRNA as determin ed by RT-PCR and cDNA sequencing, The PCR assay readily detected ppSOM mRNA in splenocytes isolated from schistosome-infected mice, but not in splenocytes from NL mice, Splenic ppSOM mRNA expression correlated with the onset of parasite egg deposition and granuloma formation, A 4 -h in vitro stimulation with LPS, rIL-10, rIFN-gamma, rTNF-alpha, pros taglandin E-2, or dibutyryl cAMP induced ppSOM mRNA in NL splenocytes that otherwise lacked this transcript, Splenocytes from severe combine d immunodeficient or recombination activating gene l-deficient mice ex pressed ppSOM after exposure to rIL-10, suggesting that neither T nor B cells are necessary for ppSOM mRNA induction, A survey of eel lines demonstrated expression of ppSOM mRNA by P388D1 and J774A.1 macrophage like cells. These data suggest that SOM, which is probably derived fro m macrophages, is an inducible component of the innate immune system t hat regulates T cell IFN-gamma production.