The CXC chemokine GCP-2/CXCL6 is predominantly induced in mesenchymal cells by interleukin-1beta and is down-regulated by interferon-gamma: comparison with interleukin-8/CXCL8.
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-1beta 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-alpha, 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-gamma down-regulated the GCP-2 production in fibroblasts induced by IL-1beta, TNF-alpha, LPS, or dsRNA. The kinetics of GCP-2 induction by IL-1beta, 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.
Wuyts
Anja
A
Laboratory of Molecular Immunology, Rega Institute, University of Leuven, Leuven, Belgium.
Struyf
Sofie
S
Gijsbers
Klara
K
Schutyser
Evemie
E
Put
Willy
W
Conings
René
R
Lenaerts
Jean-Pierre
JP
Geboes
Karel
K
Opdenakker
Ghislain
G
Menten
Patricia
P
Proost
Paul
P
Van Damme
Jo
J
D054427:Chemokine CXCL6; D019743:Chemokines, CXC / Q000096:biosynthesis*; D015536:Down-Regulation / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D007375:Interleukin-1 / Q000502:physiology*; D016209:Interleukin-8 / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics
C515503:CXCL6 protein, human; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; D007375:Interleukin-1; D016209:Interleukin-8; D007371:Interferon-gamma