The differential effects of IL-1 and TNF-alpha on proinflammatory cytokine and matrix metalloproteinase expression in human chondrosarcoma cells

Inflamm Res. 2004 Aug;53(8):377-89. doi: 10.1007/s00011-004-1271-3. Epub 2004 Aug 10.


Objective and design: Interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and matrix metalloproteinases (MMPs) play important roles in the pathogenesis of osteoarthritis (OA). In the present study, using Affymetrix oligonucleotide array technology and real-time quantitative RT-PCR we have investigated the molecular mechanisms underlying the differential effect of IL-1 and TNF-alpha on gene expression in the human chondrosarcoma cell line, SW1353.

Materials and methods: SW1353 cells were stimulated singularly with IL-1alpha, TNF-alpha, Phorbol 12-myristate 13-acetate (PMA), or treated with the combination of cytokine and PMA. Total RNA was collected at multiple time points over a 24-h period followed by biotinylated cRNA target preparation and hybridization onto the Affymetrix HG-U95Av2 array. The differential expression patterns of several cytokine and MMP genes were further confirmed by real time quantitative RT-PCR, Western blot, and ELISA.

Results: Our microarray experiments have broadly confirmed previously published data on chondrocyte gene expression regulated by IL-1 and TNF-alpha. The expression pattern of proIL-1beta, MMP-1, and MMP-13 in chondrocytes is differentially regulated when stimulated with proinflammatory cytokines. IL-1, but not TNF-alpha, can induce IL-6, bone morphogenic protein 2 (BMP-2), and cyclooxygenase (COX-2) expression in SW1353 cells. Additionally, our Western blot results provide the first evidence that IL-1beta is produced in the proform in IL-1alpha-activated chondrosarcoma cells and that additional signals are required for its posttranslational processing/activation.

Conclusions: IL-1 and TNF-alpha each activate a distinct set of genes in chondrosarcoma cells, and gene expression in these cells is regulated by groups of genes related in part by their function. Chondrocyte IL-1alpha appears to serve an important role in the pathogenesis OA contributing to joint inflammation and cartilage destruction.

MeSH terms

  • Cell Line, Tumor
  • Chondrosarcoma / enzymology
  • Chondrosarcoma / genetics*
  • Chondrosarcoma / metabolism*
  • Cluster Analysis
  • Cytokines / biosynthesis
  • Cytokines / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation Mediators / blood
  • Inflammation Mediators / metabolism
  • Interleukin-1 / biosynthesis
  • Interleukin-1 / pharmacology*
  • Matrix Metalloproteinases / biosynthesis
  • Matrix Metalloproteinases / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetradecanoylphorbol Acetate / pharmacology
  • Time Factors
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Cytokines
  • Inflammation Mediators
  • Interleukin-1
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Matrix Metalloproteinases
  • Tetradecanoylphorbol Acetate