Involvement of CXC chemokine growth-related oncogene-α in monosodium urate crystal-induced arthritis in rabbits

Kazunori Fujiwara, Susumu Ohkawara, Katsumasa Takagi, Masaru Yoshinaga, Akihiro Matsukawa

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16 Citations (Scopus)

Abstract

Accumulation of neutrophils is a prominent feature of gouty arthritis in which CXC chemokines may play a role. Recently, we have shown that IL-8 (CXCL8) contributes to neutrophil influx in a rabbit model of gouty arthritis. Here, we demonstrate that growth-related oncogene-α (GROα) (CXCL1), a prototype of CXC chemokine, is also involved in this process. GROα level in the joints peaked at 2 hours after intra-articular injection of monosodium urate crystals, at a time before the neutrophil influx reached the maximal level (9 hours). Once decreased, the level increased and reached the second peak at 9 hours. The kinetics was comparable to that of IL-8. Administration of anti-GROα mAb attenuated the neutrophil influx at the same level as did the anti-IL-8 IgG, and combination of these antibodies enhanced the inhibition, resulting in a 33% reduction. Interaction of GROα with TNFα, IL-1β, and IL-8 was next investigated by injecting antibodies or receptor antagonist with monosodium urate crystals. Administration of anti-TNFα mAb did not alter GROα level at 2 hours, but inhibited the levels 9 hours after the injection. Treatment with either IL-1 receptor antagonist or anti-IL-8 IgG resulted in decreased levels of GROa at 2 and 9 hours. Neutralization of GROα with anti-GROα mAb did not alter TNFα, IL-1β, and IL-8 levels at their peak (2 hours), but decreased the second peak of IL-1β (9 hours) and IL-8 (12 hours). These results provide evidence that GROα as well as IL-8 are involved ad eundem in the neutrophil infiltration in this model. IL-1 and IL-8, but not TNFα, are responsible in part for the initial phase of GROα, whereas these cytokines induce GROα in a late phase. GROα does not seem to initiate TNFα, IL-1β, and IL-8 in an early phase, but induces IL-1β and IL-8 in a late phase.

Original languageEnglish
Pages (from-to)1297-1304
Number of pages8
JournalLaboratory Investigation
Volume82
Issue number10
DOIs
Publication statusPublished - Oct 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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