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Overexpressed nuclear factor kappaB correlates with enhanced expression of interleukin-1beta and inducible nitric oxide synthase in aged murine lungs to endotoxic stress.

Abstract

BACKGROUND

Transcriptional regulation is a major determinant of interleukin-1beta (IL-1beta) protein synthesis. Nuclear factor kappaB (NF-kappaB) plays a central role in the regulation of IL-1beta and subsequent IL-1beta-dependent inflammatory processes. Previously, we observed in a murine endotoxic stress model a progressive increase with age in the amount of IL-1beta mRNA. We test the aging pulmonary response of NF-kappaB and NF-kappaB-dependent genes, IL-1beta, and inducible nitric oxide synthase (iNOS) in the same model.

METHODS

Young (2-month-old) and senescent (25-month-old) mice were given 0.5 mg/kg lipopolysaccharide (LPS) intraperitoneally. Lung and blood samples were harvested after 4 hours. IL-1beta production in blood samples and the expression levels of protein and mRNA of IL-1beta and iNOS in lung tissues were measured. NF-kappaB binding activity in lung tissues was also determined.

RESULTS

LPS induced higher levels of IL-1beta in the sera and lungs of senescent mice over young mice. Northern and Western blot analyses showed that mRNA and protein signals of IL-1beta and iNOS were significantly higher in old lungs than in young lungs. Electrophoretic mobility shift assay also showed that NF-kappaB activation was significantly higher in the older animals.

CONCLUSIONS

Our results suggest that elevated activation of NF-kappaB, at least in part, contributes to the dysregulated expression of IL-1beta and iNOS in the lungs of senescent animals. Thus increased expression of proinflammatory cytokines and inflammatory responsive genes in the lung may play a role in the increased susceptibility in aging animals to endotoxic stress.

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  • Authors+Show Affiliations

    ,

    Department of Surgery, Finch University of Health Sciences/The Chicago Medical School at Mount Sinai Hospital Medical Center, Chicago, Illinois, USA.

    Source

    The Annals of thoracic surgery 77:4 2004 Apr pg 1222-7; discussion 1227

    MeSH

    Aging
    Animals
    Blotting, Northern
    Blotting, Western
    Endotoxins
    Escherichia coli
    Interleukin-1
    Lipopolysaccharides
    Lung
    Mice
    Mice, Inbred Strains
    NF-kappa B
    Nitric Oxide Synthase
    Nitric Oxide Synthase Type II
    RNA, Messenger
    Shock, Septic
    Transcriptional Activation

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    15063239

    Citation

    Chang, Cheow K., and Joseph LoCicero. "Overexpressed Nuclear Factor kappaB Correlates With Enhanced Expression of Interleukin-1beta and Inducible Nitric Oxide Synthase in Aged Murine Lungs to Endotoxic Stress." The Annals of Thoracic Surgery, vol. 77, no. 4, 2004, pp. 1222-7; discussion 1227.
    Chang CK, LoCicero J. Overexpressed nuclear factor kappaB correlates with enhanced expression of interleukin-1beta and inducible nitric oxide synthase in aged murine lungs to endotoxic stress. Ann Thorac Surg. 2004;77(4):1222-7; discussion 1227.
    Chang, C. K., & LoCicero, J. (2004). Overexpressed nuclear factor kappaB correlates with enhanced expression of interleukin-1beta and inducible nitric oxide synthase in aged murine lungs to endotoxic stress. The Annals of Thoracic Surgery, 77(4), pp. 1222-7; discussion 1227.
    Chang CK, LoCicero J. Overexpressed Nuclear Factor kappaB Correlates With Enhanced Expression of Interleukin-1beta and Inducible Nitric Oxide Synthase in Aged Murine Lungs to Endotoxic Stress. Ann Thorac Surg. 2004;77(4):1222-7; discussion 1227. PubMed PMID: 15063239.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Overexpressed nuclear factor kappaB correlates with enhanced expression of interleukin-1beta and inducible nitric oxide synthase in aged murine lungs to endotoxic stress. AU - Chang,Cheow K, AU - LoCicero,Joseph,3rd PY - 2003/09/11/accepted PY - 2004/4/6/pubmed PY - 2004/5/7/medline PY - 2004/4/6/entrez SP - 1222-7; discussion 1227 JF - The Annals of thoracic surgery JO - Ann. Thorac. Surg. VL - 77 IS - 4 N2 - BACKGROUND: Transcriptional regulation is a major determinant of interleukin-1beta (IL-1beta) protein synthesis. Nuclear factor kappaB (NF-kappaB) plays a central role in the regulation of IL-1beta and subsequent IL-1beta-dependent inflammatory processes. Previously, we observed in a murine endotoxic stress model a progressive increase with age in the amount of IL-1beta mRNA. We test the aging pulmonary response of NF-kappaB and NF-kappaB-dependent genes, IL-1beta, and inducible nitric oxide synthase (iNOS) in the same model. METHODS: Young (2-month-old) and senescent (25-month-old) mice were given 0.5 mg/kg lipopolysaccharide (LPS) intraperitoneally. Lung and blood samples were harvested after 4 hours. IL-1beta production in blood samples and the expression levels of protein and mRNA of IL-1beta and iNOS in lung tissues were measured. NF-kappaB binding activity in lung tissues was also determined. RESULTS: LPS induced higher levels of IL-1beta in the sera and lungs of senescent mice over young mice. Northern and Western blot analyses showed that mRNA and protein signals of IL-1beta and iNOS were significantly higher in old lungs than in young lungs. Electrophoretic mobility shift assay also showed that NF-kappaB activation was significantly higher in the older animals. CONCLUSIONS: Our results suggest that elevated activation of NF-kappaB, at least in part, contributes to the dysregulated expression of IL-1beta and iNOS in the lungs of senescent animals. Thus increased expression of proinflammatory cytokines and inflammatory responsive genes in the lung may play a role in the increased susceptibility in aging animals to endotoxic stress. SN - 0003-4975 UR - https://www.unboundmedicine.com/medline/citation/15063239/Overexpressed_nuclear_factor_kappaB_correlates_with_enhanced_expression_of_interleukin_1beta_and_inducible_nitric_oxide_synthase_in_aged_murine_lungs_to_endotoxic_stress_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003497503021829 DB - PRIME DP - Unbound Medicine ER -