Regulation of CXCL16 expression and secretion by myeloid cells is not altered in rheumatoid arthritis.
OBJECTIVE
Chemokine (C-X-C motif) ligand 16 (CXCL16) is secreted by macrophages and dendritic cells (DCs) to attract memory type T cells. CXCL16 expression is increased in arthritic joints of patients with rheumatoid arthritis (RA) and a role for CXCL16 has been suggested in the pathogenesis of RA. To date, little is known about the regulation of CXCL16 on monocytes/macrophages and DCs. The aim of this study was to elucidate how CXCL16 expression is regulated in healthy donors and patients with RA.


METHODS
CD14+cells were isolated from the peripheral blood or synovial fluid of patients with RA and healthy controls, differentiated into different types of dendritic cells or macrophages and stimulated with various cytokines or lipopolysaccharide (LPS). Cell surface proteins, including surface CXCL16, were measured by flow cytometry and soluble CXCL16 was measured by ELISA.


RESULTS
Distinct types of dendritic cells constitutively express and secrete CXCL16, which is not affected by maturation. Monocytes rapidly upregulate membrane-bound CXCL16 expression and release soluble CXCL16 upon culture. CXCL16 expression by monocytes is transiently inhibited by the Toll-like receptor (TLR)4 ligand LPS. Th2 type cytokines inhibit soluble CXCL16, whereas T helper (Th)1 cell stimulus enhances its release. In RA monocytes/macrophages, neither CXCL16 expression, nor CXCL16 regulation is different from healthy controls.


CONCLUSIONS
Culture of monocytes is the main trigger for CXCL16 surface expression in vitro, which is not altered in RA. Together our data suggest that the increased CXCL16 expression in patients with RA is likely to be caused by increased influx of monocytes rather than intrinsic differences in CXCL16 regulation.
van Lieshout
A W T
AW
Departments of Rheumatology, Radboud University Nijmegen Medical Centre, The Netherlands.
van der Voort
R
R
Toonen
L W J
LW
van Helden
S F G
SF
Figdor
C G
CG
van Riel
P L C M
PL
Radstake
T R D J
TR
Adema
G J
GJ
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D016022:Case-Control Studies; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000032:analysis / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology; D022423:Myeloid Cells / Q000737:chemistry / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000032:analysis / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051116:Receptors, Scavenger; D007371:Interferon-gamma