doi:

DOI: 10.3724/SP.J.1206.2008.00634

Progress in Biochemistry and Biophysics (生物化学与生物物理进展) 2009/36:5 PP.574-579

The Molecular Mechanism of LPS-induced CHI3L1 Expression*


Abstract:
Treatment of chronic osteomyelitis has become a difficult problem in clinical medicine due to its extended pathological process, high occurrence of complication and recurrence of disease. The major pathogenesis mechanism is Gram-negative bacteria infection, such as staphylococci. LPS is an important substance found in the cell wall of Gram-negative bacteria and administration of LPS to skeleton relevant cells in vitro could simulate the pathological characteristics of osteomyelitis patients. The results of quantitative real-time PCR and Western blot showed that CHI3L1 was up-regulated obviously in the infected bone tissues of osteomyelitis patients and LPS-stimulated osteoblasts. Analysis of the luciferase activity of NF-κB reporter gene vector revealed that LPS could activate NF-κB. Bay11-7082, an inhibitor of NF-κB activation, suppressed the elevation of CHI3L1 expression induced by LPS. Pre-incubation of osteoblasts with anti-TNF-α antibody or silencing TNF-α receptor expression by siRNA inhibited the induction effect of LPS on CHI3L1. Inhibition of NF-κB activation also prevented up-regulation of TNF-α induced by LPS. In conclusion, LPS stimulated TNF-α expression through activating NF-κB, then TNF-α induced CHI3L1 expression. It was demonstrated for the first time that CHI3L1 expression is promoted in osteomyelitis and LPS-treated osteoblasts and investigates the molecular mechanism of LPS-induced CHI3L1 expression in osteoblasts.

Key words:osteomyelitis, LPS, CHI3L1, osteoblast

ReleaseDate:2014-07-21 14:58:07

Funds:This work was supported by a grant from The Fund for Fostering Excellent Degree Thesis in Graduate School at Shenzhen, Tsinghua University



1 Hakala B E, White C, Recklies A D. Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J Biol Chem, 1993, 268(34): 25803~25810

2 Ling H, Recklies A D. The chitinase 3-like protein human cartilage glycoprotein 39 inhibits cellular responses to the inflammatory cytokines interleukin-1 and tumour necrosis factor α. Biochem J, 2004, 380(3): 651~659

3 Østergaard C, Johansen J S, Benfield T, et al. YKL-40 is elevated in cerebrospinal fluid from patients with purulent meningitis. Clin Diagn Lab Immunol, 2002, 9(3): 598~604

4 Boot R G, van Achterberg T A, van Aken B E, et al. Strong induction of members of chitinase family proteins in atherosclerosis. Arterioscler Thromb Vasc Biol, 1999, 19 (3): 687~694

5 Chupp G L, Lee C G, Jarjour N, et al. A chitinase-like protein in the lung and circulation of patients with severe asthma. N Engl J Med, 2007, 357(20): 2016~2027

6 Hausmann E, Raisz L G, Miller W A. Endotoxin: stimulation of bone resorption in tissue culture. Science, 1970, 168(933): 861~864

7 Chiang C Y, Kyritsis G, Graves D T, et al. Interleukin-1 and tumor necrosis factor activities partially account for calvarial bone resorption induced by local injection of lipopolysaccharide. Infect Immun, 1999, 67 (8): 4231~4236

8 Caamaño J, Hunter C A. NF-κB family of transcription factors: central regulators of innate and adaptive immune functions. Clin Microbiol Rev, 2002, 15(3): 414~429

9 Tam V K, Schotland S, Green J. Inflammatory cytokines (IL-1alpha, TNF-alpha) and LPS modulate the Ca2+ signaling pathway in osteoblasts. Am J Physiol, 1998, 274 (6 Pt 1): C1686~1698

10 Recklies A D, Ling H, White C, et al. Inflammatory cytokines induce production of CHI3L1 by articular chondrocytes. J Biol Chem, 2005, 280(50): 41213~41221

11 Lew D P, Waldvogel F A. Osteomyelitis. N Engl J Med, 1997, 336(14): 999~1007

12 Cunningham R, Cockayne A, Humphreys H. Clinical and molecular aspects of the pathogenesis of Staphylococcus aureus bone and joint infections. J Med Microbiol, 1996, 44(3): 157~164

13 Papin S, Cazeneuve C, Duquesnoy P, et al. The tumor necrosis factor alpha-dependent activation of the human mediterranean fever (MEFV) promoter is mediated by a synergistic interaction between C/EBP beta and NF kappaB p65. J Biol Chem, 2003, 278(49): 48839~48847

14 Miyazawa K, Mori A, Yamamoto K, et al. Transcriptional roles of CCAAT/enhancer binding protein-beta, nuclear factor-kappaB, and C-promoter binding factor 1 in interleukin (IL)-1beta-induced IL-6 synthesis by human rheumatoid fibroblast-like synoviocytes. J Biol Chem, 1998, 273(13): 7620~7627

15 Yoshii T, Magara S, Miyai D, et al. Local levels of interleukin-1beta, -4, -6 and tumor necrosis factor alpha in an experimental model of murine osteomyelitis due to staphylococcus aureus. Cytokine, 2002, 21(2): 59~65

PDF