LIPOPOLYSACCHARIDE UP-REGULATES PLATELET-DERIVED GROWTH-FACTOR (PDGF)ALPHA-RECEPTOR EXPRESSION IN RAT LUNG MYOFIBROBLASTS AND ENHANCES RESPONSE TO ALL PDCF ISOFORMS

Differential expression of PDGF receptor alpha and beta subunits contr ols the response of mesenchymal cells to the three PDGF isoforms (AA, AB, and BB). Cultured rat lung myofibroblasts (RLMF) possess abundant PDGF receptor-beta (PDGF-R beta) and little PDGF receptor-alpha (PDGF- R alpha). Here we show that LPS up-regulates expression of PDGF-R alph a and increases the sensitivity of RLMF to all three PDGF isoforms. Tr eatment of RLMF for 4 to 48 h with LPS enhanced PDGF-R alpha surface e xpression and mRNA 5- to 10-fold but caused no change in expression of PDGF-RP, Both RNA and protein synthesis were necessary for up-regulat ion of PDGF-R alpha, and the increase in PDGF-R alpha mRNA was most li kely regulated at the transcriptional level, PDGF-R alpha up-regulatio n was not mediated by the IL-1R system and was independent of LPS-bind ing proteins in serum, Highly confluent cultures of RLMF responded mor e strongly to LPS than did subconfluent cultures. LPS treatment enhanc ed the mitogenic and chemotactic responses of RLMF to all PDGF isoform s at least threefold. We postulate that signal transduction by PDGF-re ceptor cup heterodimers was important in the enhanced responses to PDG F-AB and -BB. We propose that regulation of PDGF-R alpha is a critical event in the genesis of pulmonary fibroproliferative diseases.