The effects of interleukin-18 on rat articular chondrocytes

A study of mRNA expression and protein synthesis of proinflammatory substances

X. J. Ye, B. Tang, Z. Ma, J. Zhou, Linda Myers, Andrew Kang, M. A. Cremer

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Interleukin (IL)-18 is a potent stimulator of immunity and augments the severity of type II collagen-induced arthritis (CIA) in rats and mice by enhancing T helper 1 (Th1) cell activation, which increases the production of proinflammatory cytokines and arthritogenic antibodies. In this study, we show that recombinant IL-18 (rIL-18) also has a direct effect on normal rat chondrocytes maintained in vitro inducing them to produce proinflammatory factors including IL-6, regulated upon activation normal T cell expressed and secreted (RANTES), prostaglandin E2 (PGE2) and prostaglandin F (PGF) in a dose- and time-dependent manner. The production of matrix metalloproteinase (MMP)-13, nitric oxide (NO), tumour necrosis factor (TNF)-α and IL-1β were also enhanced, although less intensely. Neutralizing polyclonal anti-rIL-18 antibodies effectively blocked the production of IL-6, PGE2 and RANTES, as well as mRNA expression for the same products in addition to IL-18 and TNF-α. In contrast, neutralizing antibodies to IL-1β, TNF-α and IL-6 were ineffective in suppressing any of these products. Together, these findings suggest that IL-18 may play an important, possibly direct, role in mediating cartilage injury, which might not be amenable to treatment with currently utilized anti-cytokine agents. These findings suggest further that IL-18 antagonists might prove beneficial as anti-inflammatory and chondroprotective agents in the treatment of arthritis, and that the development of such agents for human use is worth consideration.

Original languageEnglish (US)
Pages (from-to)553-560
Number of pages8
JournalClinical and Experimental Immunology
Volume149
Issue number3
DOIs
StatePublished - Sep 1 2007

Fingerprint

Interleukin-18
Chondrocytes
Joints
Messenger RNA
Interleukin-6
Proteins
Tumor Necrosis Factor-alpha
Interleukin-1
Dinoprostone
Matrix Metalloproteinase 13
Cytokines
T-Lymphocytes
Th1 Cells
Experimental Arthritis
Dinoprost
Antibodies
Neutralizing Antibodies
Arthritis
Cartilage
Immunity

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

The effects of interleukin-18 on rat articular chondrocytes : A study of mRNA expression and protein synthesis of proinflammatory substances. / Ye, X. J.; Tang, B.; Ma, Z.; Zhou, J.; Myers, Linda; Kang, Andrew; Cremer, M. A.

In: Clinical and Experimental Immunology, Vol. 149, No. 3, 01.09.2007, p. 553-560.

Research output: Contribution to journalArticle

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