Post-transcriptional regulation of chymase expression in mast cells. A cytokine-dependent mechanism for controlling the expression of granule neutral proteases of hematopoietic cells.

Although all mouse mast cells are derived from a common progenitor, these effector cells exhibit tissue-specific differences in their expression of the chymase family of serine proteases whose genes reside on chromosome 14. Immature bone marrow-derived mast cells (mBMMC), developed in vitro with interleukin (IL) 3-enriched medium, were cultured in the presence or absence of IL-10 to determine at the molecular level how the expression of the individual chymases is differentially regulated. As assessed by RNA blot analysis, mBMMC contain high steady-state levels of the transcript that encodes mouse mast cell protease (mMCP) 5, but not the homologous chymase transcripts that encode mMCP-1, mMCP-2, or mMCP-4. Nevertheless, nuclear run-on analysis revealed that these cells transcribe all four mast cell chymase genes. IL-10 elicited high steady-state levels of the mMCP-2 transcript, and pulse-chase experiments revealed that the half-life of the mMCP-2 transcript in mBMMC maintained in the presence of IL-10 is approximately 4-fold longer than that in replicate cells subsequently cultured in medium without IL-10. Reverse transcription-polymerase chain reaction/nucleotide sequence analysis demonstrated that mBMMC cultured in the absence or presence of IL-10 correctly process mMCP-2 pre-mRNA. Experiments with cycloheximide and actinomycin D indicated that IL-10 induces expression of a trans-acting factor(s) that stabilizes the mMCP-2 transcript or facilitates its processing. The discovery that the expression of certain chymases in mBMMC is regulated primarily at the post-transcriptional level provides a basis for understanding the mechanism by which specific cytokines dictate expression of the chromosome 14 family of serine proteases in cells that participate in inflammatory processes.