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Parathyroid hormone (1-34)-mediated interleukin-6 induction
J E Onyia1, T A Libermann, J Bidwell
1Endocrine Division, Lilly Research Labs, Indianapolis, Indiana 46285, USA.
Journal of Cellular Biochemistry
|November 5, 1997
Summary
Parathyroid hormone (PTH) stimulates interleukin-6 (IL-6) gene transcription in bone cells. This effect is mediated by the cAMP-protein kinase A pathway, similar to forskolin, and is also induced by IL-1 alpha.
Area of Science:
- Molecular Endocrinology
- Cell Biology
- Bone Biology
Background:
- Parathyroid hormone (PTH) is a key regulator of calcium homeostasis and bone metabolism.
- PTH influences cytokine expression in osteoblasts, the cells responsible for bone formation.
- Previous research indicated PTH rapidly increases interleukin-6 (IL-6) mRNA in rat bone.
Purpose of the Study:
- To investigate the molecular mechanisms by which PTH regulates IL-6 gene expression.
- To compare the effects of PTH on IL-6 promoter activity with other signaling molecules.
Main Methods:
- Utilized a reporter gene assay with the human IL-6 promoter (-1,179 to +9) linked to a CAT gene.
- Transfected the construct into human osteosarcoma SaOS-2 cells (osteoblast-like).
- Treated cells with PTH, forskolin, IL-1 alpha, RS-66271, PMA, A23187, PGE-2, and PDGF-BB.
Main Results:
- PTH dose-dependently increased IL-6 promoter activity (200-500%).
- Interleukin-1 alpha (IL-1 alpha) was a more potent inducer (900-1,000%).
- Forskolin and RS-66271 (PTH analog) mimicked PTH's effect, suggesting cAMP-PKA pathway involvement; effects were additive with PTH.
- PGE-2, PMA, PDGF-BB, and A23187 did not significantly alter IL-6 promoter activity.
Conclusions:
- PTH, IL-1 alpha, forskolin, and RS-66271 stimulate IL-6 gene transcription.
- The cAMP-protein kinase A (PKA) pathway is sufficient for mediating PTH-induced IL-6 expression.
- PTH regulates IL-6 expression at the transcriptional level in osteoblast-like cells.