ISOLATION OF 9 GENE-SEQUENCES INDUCED BY SILICA IN MURINE MACROPHAGES

Macrophage activation by silica is the initial step in the development of silicosis. To identify genes that might be involved in silica-medi ated activation, RAW 264.7 mouse macrophages were treated with silica for 48 h, and a subtracted cDNA library enriched for silica-induced ge nes (SIG) was constructed and differentially screened. Nine cDNA clone s (designated SIG-12, -14, -20, -41, -67, -87, -97, -92, and -111) wer e partially sequenced and compared with sequences in GenBank/EMBL data bases. SIG-12, -14, and -20 corresponded to the genes for ribosomal pr oteins L13a, L32, and L26, respectively. SIG-61 is the mouse homologue of p21 RhoC. SIG-91 is identical to the 67-kDa high-affinity laminin receptor. Four genes were not identified and are novel. All of the mRN As corresponding to the nine cloned cDNAs were inducible by silica. St eady-state levels of mRNAs in RAW 264.7 cells treated with various mac rophage activators and inducers of signal transduction pathways were d etermined. A complex pattern of induction and repression was found, in dicating that upon phagocytosis of silica particles, many regulatory m echanisms of gene expression are simultaneously triggered.