These authors contributed equally to this work as first authors.
Mechanical stress-activated immune response genes via Sirtuin 1 expression in human periodontal ligament cells
Article first published online: 2 MAR 2012
© 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology
Clinical & Experimental Immunology
Volume 168, Issue 1, pages 113–124, April 2012
How to Cite
Lee, S.-I., Park, K.-H., Kim, S.-J., Kang, Y.-G., Lee, Y.-M. and Kim, E.-C. (2012), Mechanical stress-activated immune response genes via Sirtuin 1 expression in human periodontal ligament cells. Clinical & Experimental Immunology, 168: 113–124. doi: 10.1111/j.1365-2249.2011.04549.x
- Issue published online: 2 MAR 2012
- Article first published online: 2 MAR 2012
- Accepted manuscript online: 21 DEC 2011 01:34PM EST
- Accepted for publication 14 December 2011
- immune genes;
- mechanical stress;
- periodontal ligament cells;
Recently, Sirtuin 1 (SIRT1) has been implicated in the molecular control of ageing and immune response. Although the remodelling of periodontal ligament (PDL) in response to mechanical stress (MS) is mediated by several host factors, including cytokines and chemokines, the transmission of mechanical stimuli into specific cellular activity is still not understood fully. This study aimed to investigate the effects of MS, particularly cyclic strain, on immune response genes, as well as SIRT1 and its signal transduction pathways, in human PDL cells. MS up-regulated the expression of SIRT1 and immune response genes encoding cytokines [tumour necrosis factor (TNF)-α, interleukin (IL)-1β], chemokines [IL-8, monocyte cheoattractant protein (CCL)-20], defensins [human β-defensin (hBD)-2, hBD-3] and Toll-like receptors (TLR-2 and TLR-4) in a force- and time-dependent manner. The SIRT1 inducers resveratrol and isonicotinamide attenuated MS-induced cytokine and chemokine expression, but enhanced the expression of defensins and TLRs. Blockade of SIRT1 activity by the SIRT1 inhibitors sirtinol and nicotinamide and down-regulation of SIRT1 expression by SIRT1 siRNA reduced the stimulatory effects of MS on defensins and TLRs, but increased its effects on cytokines and chemokines. MS induced activation of protein kinase B (Akt), protein kinase C (PKC), nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Treatment with the anti-oxidants N-acetylcysteine and glutathione inhibited MS-induced reactive oxygen species production and expression of cytokines, chemokines, defensins and TLRs. These results suggest that MS activates human PDL cells to express immune/defence genes encoding cytokines, chemokines, defensins and TLRs via a SIRT1 pathway.