The CXC Chemokine GCP-2/CXCL6 Is Predominantly Induced in Mesenchymal Cells by Interleukin-1β and Is Down-Regulated by Interferon-γ: Comparison with Interleukin-8/CXCL8

Abstract

SUMMARY:Human granulocyte chemotactic protein-2 (GCP-2)/CXCL6 is a CXC chemokine that functionally uses both of the IL-8/CXCL8 receptors to chemoattract neutrophils but that is structurally most related to epithelial cell-derived neutrophil attractant-78 (ENA-78)/CXCL5. This study provides the first evidence that GCP-2 protein is, compared with IL-8, weakly produced by some sarcoma, but less by carcinoma cells, and is tightly regulated in normal mesenchymal cells. IL-1␤ was the predominant GCP-2 inducer in fibroblasts, chondrocytes, and endothelial cells, whereas IL-8 was equally well up-regulated in these cells by TNF-␣, measles virus, or double-stranded RNA (dsRNA). In contrast, lipopolysaccharide (LPS) was a relatively better stimulus for GCP-2 versus IL-8 in fibroblasts. IFN-␥ down-regulated the GCP-2 production in fibroblasts induced by IL-1␤, TNF-␣, LPS, or dsRNA. The kinetics of GCP-2 induction by IL-1␤, LPS, or dsRNA in fibroblasts differed from those of IL-8. Freshly isolated peripheral blood mononuclear leukocytes, which are a good source of IL-8 and ENA-78, failed to produce GCP-2. However, lung macrophages and blood monocyte-derived macrophages produced GCP-2 in response to LPS. Quantitatively, secretion of GCP-2 always remained inferior to that of IL-8, despite the fact that the ELISA recognized all posttranslationally modified GCP-2 isoforms. The expression of GCP-2 was confirmed in vivo by immunohistochemistry. The patterns of producer cell types, inducers and kinetics and the quantities of GCP-2 produced, suggest a unique role for GCP-2 in physiologic and pathologic processes. (Lab Invest 2003, 83:23-34).

Exacerbation of Antigen-Induced Arthritis in IFN-γ-Deficient Mice As a Result of Unrestricted IL-17 Response

“…Next to lymphocyte recruitment, IFN-␥ also affects inflammatory neutrophil recruitment. Production of neutrophil attracting and activating chemokine granulocyte chemotactic protein-2 by stimulated human fibroblasts and murine macrophage-derived KC and MIP-2 are down-regulated by IFN-␥ (43,44). In vitro studies using RA fibroblasts demonstrated IFN-␥ to significantly reduce neutrophil-activating chemokine CXCL8 generation induced by IL-1␤ or TNF-␣, but in contrast increase CCL2 production (45).…”

Differential inlA and inlB Expression and Interaction with Human Intestinal and Liver Cells by Listeria monocytogenes Strains of Different Origins

“…The concentration of IL-8 in the culture supernatant of the infected cells was determined by enzyme-linked immunosorbent assay (ELISA). For IL-8 detection, a polyclonal goat anti-human IL-8 antibody for coating (61) and a monoclonal mouse anti-human IL-8 antibody (R&D Systems, Abingdon, United Kingdom) were used as described previously (68). As a positive control for IL-8 production, cells were stimulated for 24 h with 5 g/l lipopolysaccharide (LPS) (Escherichia coli O111:B4) (Difco Laboratories, Detroit, Mich.).…”

Production and upregulation of granulocyte chemotactic protein-2/CXCL6 by IL-1β and hypoxia in small cell lung cancer

“…Regulation of granulocyte chemotactic protein-2 secretion by IL-1b IL-1b has been shown to be the predominant inducer of GCP-2 in non-tumour cells such as mesenchymal cells (Wuyts et al, 2003) and endometrial stromal cells (Mine et al, 2003). To assess whether IL-1b induces GCP-2 in SCLC cell lines, the high-GCP-2-producing H345 and H711 cells were treated by rIL-1b at a final concentration of 0.1 or 1 ng ml À1 for 24 h ( Figure 3A).…”