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Differential regulation of M‐CSF and IL‐6 gene expression in monocytic cells
Author(s) -
Wit Harry,
Esselink Mariet T.,
Halie M. Ruud,
Vellenga Edo
Publication year - 1994
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1994.tb04724.x
Subject(s) - protein kinase c , gene expression , messenger rna , microbiology and biotechnology , downregulation and upregulation , regulation of gene expression , biology , signal transduction , stimulation , transcriptional regulation , protein kinase a , kinase , second messenger system , gene , endocrinology , biochemistry
Summary Using the human monocytic cell line Mono Mac 6 we studied the involvement of Ca 2+ , protein kinase A (PKA), and protein kinase C (PKC) dependent pathways in the regulation of M‐CSF and IL‐6 gene expression. The results demonstrate that on activation with the calcium ionophore A23187 both M‐CSF and IL‐6 mRNA are induced after 3 and 6 h respectively. Co‐stimulation with A23187 plus PMA resulted in an up‐regulation of M‐CSF mRNA and a downregulation of IL‐6 mRNA. Conversely co‐stimulation with A23187 plus DBcAMP resulted in a down‐regulation of M‐CSF mRNA and an up‐regulation of IL‐6 mRNA. Nuclear run‐on and mRNA half‐life studies showed that the effects on the M‐CSF expression were related to changes at transcriptional and post‐transcriptional level. In contrast, the effects on the IL‐6 gene expression seems to be mediated at post‐transcriptional level. With regard to the secretion of the IL‐6 protein it was shown that it closely follows the accumulation of IL‐6 mRNA. Taken together, the data show that several intracellular signalling pathways control strictly the cytokine expression in monocytic cells which gives the cells the opportunity to respond variably to external activation signals.