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Detection of elevated N epsilon-carboxymethyllysine levels in muscular tissue and in serum of patients with fibromyalgia.

Abstract

OBJECTIVES

To compare levels of the advanced glycation end product (AGE) N(epsilon)-carboxymethyllysine (CML) present in the muscle tissue and in the serum of patients with fibromyalgia (FM) vs. healthy controls.

METHODS

The serum levels of CML were measured in 41 patients with FM and 81 healthy controls. The presence of CML, nuclear factor kappa B (NF-kappaB), the AGE receptor (RAGE), collagen types I, II, VI, and CD68-positive monocytes/macrophages in muscle tissue of 14 patients with FM was investigated by immunohistochemistry.

RESULTS

Patients with FM showed significantly increased serum levels of CML in comparison to healthy controls. The immunohistochemical investigation revealed a stronger staining for CML and NF-kappaB and more CD68-positive monocytes/macrophages in the muscle of FM patients. The collagens and CML were co-localized, suggesting that the AGE modifications were related to collagen. RAGE was absent in controls but a faint and patchy staining was seen in FM.

CONCLUSIONS

In the interstitial connective tissue of fibromyalgic muscles we found a more intensive staining of the AGE CML, activated NF-kappaB, and also higher CML levels in the serum of these patients compared to the controls. RAGE was only present in FM muscle. AGE modification of proteins causes reduced solubility and high resistance to proteolytic digestion of the altered proteins (e.g. AGE-modified collagens). AGEs can stimulate different types of cells by activation of the transcription factor NF-kappaB, mediated by specific receptors of AGEs (e.g. RAGE) on the cell surface. Both mechanisms may contribute to the development, perpetuation, and spreading of pain characteristic in FM patients.

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  • Authors+Show Affiliations

    ,

    Department of Internal Medicine III, Friedrich-Schiller-University of Jena, Germany. Michael.Ruester@med.uni-jena.de

    , , , ,

    Source

    MeSH

    Adult
    Antigens, CD
    Antigens, Differentiation, Myelomonocytic
    Case-Control Studies
    Collagen
    Female
    Fibromyalgia
    Glycation End Products, Advanced
    Humans
    Immunohistochemistry
    Lysine
    Male
    Middle Aged
    Muscles
    NF-kappa B
    Receptor for Advanced Glycation End Products
    Receptors, Immunologic

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    16393769

    Citation

    Rüster, M, et al. "Detection of Elevated N Epsilon-carboxymethyllysine Levels in Muscular Tissue and in Serum of Patients With Fibromyalgia." Scandinavian Journal of Rheumatology, vol. 34, no. 6, 2005, pp. 460-3.
    Rüster M, Franke S, Späth M, et al. Detection of elevated N epsilon-carboxymethyllysine levels in muscular tissue and in serum of patients with fibromyalgia. Scand J Rheumatol. 2005;34(6):460-3.
    Rüster, M., Franke, S., Späth, M., Pongratz, D. E., Stein, G., & Hein, G. E. (2005). Detection of elevated N epsilon-carboxymethyllysine levels in muscular tissue and in serum of patients with fibromyalgia. Scandinavian Journal of Rheumatology, 34(6), pp. 460-3.
    Rüster M, et al. Detection of Elevated N Epsilon-carboxymethyllysine Levels in Muscular Tissue and in Serum of Patients With Fibromyalgia. Scand J Rheumatol. 2005;34(6):460-3. PubMed PMID: 16393769.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Detection of elevated N epsilon-carboxymethyllysine levels in muscular tissue and in serum of patients with fibromyalgia. AU - Rüster,M, AU - Franke,S, AU - Späth,M, AU - Pongratz,D E, AU - Stein,G, AU - Hein,G E, PY - 2006/1/6/pubmed PY - 2006/3/29/medline PY - 2006/1/6/entrez SP - 460 EP - 3 JF - Scandinavian journal of rheumatology JO - Scand. J. Rheumatol. VL - 34 IS - 6 N2 - OBJECTIVES: To compare levels of the advanced glycation end product (AGE) N(epsilon)-carboxymethyllysine (CML) present in the muscle tissue and in the serum of patients with fibromyalgia (FM) vs. healthy controls. METHODS: The serum levels of CML were measured in 41 patients with FM and 81 healthy controls. The presence of CML, nuclear factor kappa B (NF-kappaB), the AGE receptor (RAGE), collagen types I, II, VI, and CD68-positive monocytes/macrophages in muscle tissue of 14 patients with FM was investigated by immunohistochemistry. RESULTS: Patients with FM showed significantly increased serum levels of CML in comparison to healthy controls. The immunohistochemical investigation revealed a stronger staining for CML and NF-kappaB and more CD68-positive monocytes/macrophages in the muscle of FM patients. The collagens and CML were co-localized, suggesting that the AGE modifications were related to collagen. RAGE was absent in controls but a faint and patchy staining was seen in FM. CONCLUSIONS: In the interstitial connective tissue of fibromyalgic muscles we found a more intensive staining of the AGE CML, activated NF-kappaB, and also higher CML levels in the serum of these patients compared to the controls. RAGE was only present in FM muscle. AGE modification of proteins causes reduced solubility and high resistance to proteolytic digestion of the altered proteins (e.g. AGE-modified collagens). AGEs can stimulate different types of cells by activation of the transcription factor NF-kappaB, mediated by specific receptors of AGEs (e.g. RAGE) on the cell surface. Both mechanisms may contribute to the development, perpetuation, and spreading of pain characteristic in FM patients. SN - 0300-9742 UR - https://www.unboundmedicine.com/medline/citation/16393769/Detection_of_elevated_N_epsilon_carboxymethyllysine_levels_in_muscular_tissue_and_in_serum_of_patients_with_fibromyalgia_ L2 - http://www.tandfonline.com/doi/full/10.1080/03009740510026715 DB - PRIME DP - Unbound Medicine ER -