Functional distinction between CXC chemokines, interleukin-8 (IL-8), and growth related oncogene (GRO)α in neutrophil infiltration

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Interleukin-8 (IL-8: CXCL8) and growth related oncogene α (GROα: CXCL1) are members of the CXC chemokines. In the present study, we explored the functional distinction between these CXC chemokines in the regulation of neutrophil infiltration. Injection of either rabbit IL-8 or GROα (10 μg each) into rabbit knee joints resulted in a massive neutrophil infiltration in the joints. At their peak time point (6 hours), the number of neutrophils induced by IL-8 was more than that induced by GROα. Each chemokine induced the other chemokine in the joints. TNFα activity was induced in the joints after administration of GROα, but not IL-8. Treatment with anti-GROα mAb and/or anti-TNFα mAb failed to inhibit IL-8-induced neutrophil infiltration. In contrast, either anti-IL-8 IgG or anti-TNFα mAb decreased GROα-induced response, and the inhibition was further enhanced by coadministration of these antibodies. Thus, it appears that IL-8 acts directly, whereas GROα acts indirectly, in part, on neutrophil infiltration. The distinct difference in TNFα production between IL-8 and GROα was further investigated. In vitro, GROα induced TNFα activity in cultured synovial cells, the cells producing TNFα in the joints after GROα-injection. However, IL-8 failed to produce TNFα activity from the cells, although equivalent levels of the mRNA expression were induced by IL-8 as compared with GROα. When recombinant rabbit TNFα was incubated with synovial fluids obtained at 2 hours after IL-8 injection, the resultant TNFα activity was significantly decreased, an event that was completely restored by a serine protease inhibitor, phenylmethylsulphonyl fluoride (PMSF). Furthermore, TNFα activity was unveiled in the joints when IL-8 was intra-articularly injected with PMSF. These data suggest that TNFα is degraded by serine protease(s) in the case of IL-8. Taken together, the data clearly demonstrate the functional distinction between IL-8 and GROα, which may influence the inflammatory responses.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalLaboratory Investigation
Volume82
Issue number1
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

CXC Chemokines
Neutrophil Infiltration
Interleukin-8
Oncogenes
Growth
Joints
Rabbits
Fluorides
Chemokines
Injections
Serine Proteinase Inhibitors
Synovial Fluid
Serine Proteases
Knee Joint

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Functional distinction between CXC chemokines, interleukin-8 (IL-8), and growth related oncogene (GRO)α in neutrophil infiltration. / Fujiwara, Kazunori; Matsukawa, Akihiro; Ohkawara, Susumu; Takagi, Katsumasa; Yoshinaga, Masaru.

In: Laboratory Investigation, Vol. 82, No. 1, 2002, p. 15-23.

Research output: Contribution to journalArticle

Fujiwara, Kazunori ; Matsukawa, Akihiro ; Ohkawara, Susumu ; Takagi, Katsumasa ; Yoshinaga, Masaru. / Functional distinction between CXC chemokines, interleukin-8 (IL-8), and growth related oncogene (GRO)α in neutrophil infiltration. In: Laboratory Investigation. 2002 ; Vol. 82, No. 1. pp. 15-23.
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