geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Telomere-mediated chromosomal instability triggers TLR4 induced inflammation and death in mice


, : Telomere-mediated chromosomal instability triggers TLR4 induced inflammation and death in mice. Plos One 5(7): E11873-E11873

Telomeres are essential to maintain chromosomal stability. Cells derived from mice lacking telomerase RNA component (mTERC-/- mice) display elevated telomere-mediated chromosome instability. Age-dependent telomere shortening and associated chromosome instability reduce the capacity to respond to cellular stress occurring during inflammation and cancer. Inflammation is one of the important risk factors in cancer progression. Controlled innate immune responses mediated by Toll-like receptors (TLR) are required for host defense against infection. Our aim was to understand the role of chromosome/genome instability in the initiation and maintenance of inflammation. We examined the function of TLR4 in telomerase deficient mTERC-/- mice harbouring chromosome instability which did not develop any overt immunological disorder in pathogen-free condition or any form of cancers at this stage. Chromosome instability was measured in metaphase spreads prepared from wildtype (mTERC+/+), mTERC+/- and mTERC-/- mouse splenocytes. Peritoneal and/or bone marrow-derived macrophages were used to examine the responses of TLR4 by their ability to produce inflammatory mediators TNFalpha and IL6. Our results demonstrate that TLR4 is highly up-regulated in the immune cells derived from telomerase-null (mTERC-/-) mice and lipopolysaccharide, a natural ligand for TLR4 stabilises NF-kappaB binding to its promoter by down-regulating ATF-3 in mTERC-/- macrophages. Our findings implied that background chromosome instability in the cellular level stabilises the action of TLR4-induced NF-kappaB action and sensitises cells to produce excess pro-inflammatory mediators. Chromosome/genomic instability data raises optimism for controlling inflammation by non-toxic TLR antagonists among high-risk groups.

US$19.90

PMID: 20686699

DOI: 10.1371/journal.pone.0011873


Other references

Sodipo, J.O., 1968: Regional block for circumcision in adults. West African Medical Journal and Nigerian Practitioner 17(6): 177-178

Connor, E.; Sperling, R.; Shapiro, D.; Oleske, J.; Fowler, M.G.; Groups, T.P.otocol 076 And 2 tudy, 1995: Long term effect of zidovudine exposure among uninfected infants born to HIV-infected mothers in pediatric AIDS clinical trials group protocol 076. Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 35(0): 205

Asakura, R.; Matsuwaki, T.; Shim, J-Hyun.; Yamanouchi, K.; Nishihara, M., 2012: Involvement of progranulin in the enhancement of hippocampal neurogenesis by voluntary exercise. We have previously suggested that progranulin mediates the stimulatory effects of estrogen on adult neurogenesis in the hippocampus. Neurogenesis in mature animals is enhanced by growth factors, environmental enrichment, and voluntary exercise. In...

Park, E.; Smucker, A., 2005: Saturated hydraulic conductivity and porosity within macroaggregates modified by tillage. Greater knowledge of intraaggregate porosity modifications by tillage conveys new information for identifying additional hydrologic, ion retention, and aggregate stability responses to specific management practices. Macroaggregates, 2 to 4, 4 to 6...

Anonymous, 2005: Abstracts of the American Association for Cancer Education 39th Annual Meeting. September 15-17, 2005, Cincinnati, Ohio, USA. Journal of Cancer Education 20(3 Suppl): 12-42

Luo, S.L., 1988: Comparative study on the effects of 5 disinfection methods on the hepatitis B virus in patients' serum. Zhonghua Hu Li Za Zhi 23(4): 224-226

Baldwin, L.C., 1990: Child abuse as an antecedent of multiple personality disorder. Until recently, few cases of multiple personality disorder were diagnosed in children. Today, the number of cases is increasing at an alarming rate and appears to be most closely associated with repeated sexual and physical abuse. This paper focus...

Yi, J.B.; Kim, Y.T.; Bae, H.J.; Whiteside, W.S.; Park, H.J., 2006: Influence of transglutaminase-induced cross-linking on properties of fish gelatin films. Fish gelatin (FG) is a potential alternative to current mammalian (beef and pork) gelatin. However, its physical and thermal properties limit its use in many applications. The treatment of microbial transglutaminase (MTGase) on FG could be a prac...

Sperling, M.; Chen, I.Wen; Flitman, H.; Ghosn, S.; Gibler, W.B.ian, 1995: Serum cardiac troponin-T in patients with elevated serum creatinine concentration. Clinical Chemistry 41(S6 PART 2): S166

Katlama, C.; Gazzard, B.; Mallolas, J.; Schürmann, D.; Moroni, M.; Demonty, N.; Antoun, Z.; Gordon, D., 2003: Comparison of metabolic abnormalities 48 weeks after switching from highly active antiretroviral therapy containing a non-nucleoside reverse transcriptase inhibitor to Trizivir versus continued highly active antiretroviral therapy. Forty patients participating in the TRIZAL study were treated with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimen before being randomly assigned either to continue their baseline therapy or to switch to a triple nucleo...