Expression of High Mobility Group Box Chromosomal Protein 1 and Its Modulating Effects on Downstream Cytokines in Systemic Lupus Erythematosus

Department of Dermatology, Xiangya Hospital, Central South University, Hunan, China.
The Journal of Rheumatology (Impact Factor: 3.17). 04/2010; 37(4):766-75. DOI: 10.3899/jrheum.090663
Source: PubMed

ABSTRACT To compare the expression of high mobility group box chromosomal protein 1 (HMGB1) and the modulating effects on its downstream cytokines in patients with systemic lupus erythematosus (SLE) and healthy controls.
HMGB1 concentrations in serum from SLE patients and controls were measured by immunoblot analysis. HMGB1 messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMC) was detected by real-time reverse transcription-polymerase chain reaction. Immunofluorescence assay was employed to examine the translocation of HMGB1 in monocytes after endotoxin stimulation. Release of tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) by PBMC after rHMGB1 stimulation was also measured.
Serum HMGB1 levels and HMGB1 mRNA expressions in PBMC were elevated in SLE patients compared with controls. A positive correlation was demonstrated between HMGB1 concentrations and SLE Disease Activity Index. There was an inverse correlation between HMGB1 levels and C4 and C3 concentrations in SLE patients. HMGB1 concentrations were higher in patients with vasculitis and myositis. Lipopolysaccharide stimulated a temporarily elevated release of HMGB1 in SLE patients compared with controls. The pattern and localization of HMGB1 staining in monocytes were similar in both groups. After stimulation with rHMGB1, TNF-alpha level decreased but IL-6 level increased in SLE patients compared with controls.
Our findings suggest that increased serum levels of HMGB1 in SLE may be associated with lupus disease activity. The altered production of TNF-alpha and IL-6 in response to rHMGB1 stimulation may participate in the disruption of cytokine homeostasis in SLE.

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    • "In SLE, HMGB1 was demonstrated to be associated with nucleosomes released from apoptotic cells and to contribute to the immunostimulatory effect of nucleosomes (Urbonaviciute et al. 2008). In addition, HMGB1 has been found to be significantly elevated in lupus sera and has been regarded as one of the components in DNA-containing immune complexes that enhance cytokine production (Li et al. 2010). "
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    • "Among the beneficial roles of the protein, it is to be mentioned also the promotion of tissue regeneration, realized by attracting stem cells and inducing their proliferation (Degryse et al., 2001). However, HMGB1 has been proposed to contribute to the pathogenesis of various chronic inflammatory and autoimmune diseases (Scaffidi et al., 2002; Palumbo et al., 2004; Wang et al., 2004; Pisetsky et al., 2008; Voll et al., 2008; Andersson & Harris, 2010), and high serum levels of HMGB1 have been found in several inflammatory events, including sepsis (Sunden-Cullberg et al., 2005), rheumatoid arthritis (Goldstein et al., 2007; Andersson & Harris, 2010), atherosclerosis (Li et al., 2006), chronic kidney disease (Bruchfeld et al., 2008), systemic lupus erythematosus (SLE) (Jiang & Pisetsky, 2008; Li et al., 2010; Urbonaviciute & Voll, 2011), as well as in cancer pathogenesis (Ellerman at al., 2007; Tang et al., 2010b). In particular, high expression of HMGB1 was observed in certain primary tumors including melanoma and colon, prostate, pancreatic , and breast cancers (Ellerman at al., 2007). "
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