Soluble CD93 induces differentiation of monocytes and enhances TLR responses.
The cell surface protein CD93 is known to be involved in the regulation of phagocytosis and cell adhesion. Although typically membrane-bound, a soluble form of CD93 (sCD93) has recently been identified. Currently, however, the role of sCD93 in monocyte function is unknown. In the current study, we analyzed the functional effects of sCD93 on THP-1 monocytic cells and human primary monocytes. Various forms of recombinant human sCD93 were used to investigate the effects of this molecule on both human primary monocytes and a monocytic cell line, THP-1. We found that sCD93 induced differentiation of monocytes to macrophage-like cells, as evidenced by activated cell adhesion and increased phagocytic activities. In addition, this differentiation resulted in an enhanced response to TLR stimulation in terms of differentiation marker expression and proinflammatory cytokine production. Furthermore, sCD93 enhanced LPS-stimulated TNF-α production even prior to monocyte differentiation. To investigate a possible role for sCD93 in the pathogenesis of chronic inflammatory diseases, we assessed the concentration of sCD93 in synovial fluid from patients with rheumatoid arthritis and found it to be significantly increased compared with synovial fluid from patients with osteoarthritis. Together, these data revealed a function for sCD93 that may have implications in inflammation and inflammatory diseases including rheumatoid arthritis.
Jeon
Jae-Won
JW
Nucleic Acid Biochemistry Laboratory, Department of Biological Science, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Jung
Joon-Goo
JG
Shin
Eui-Cheol
EC
Choi
Hye In
HI
Kim
Ho Youn
HY
Cho
Mi-La
ML
Kim
Sun-Wha
SW
Jang
Young-Soon
YS
Sohn
Myung-Ho
MH
Moon
Ji-Hyun
JH
Cho
Young-Hun
YH
Hoe
Kwang-Lae
KL
Seo
Yeon-Soo
YS
Park
Young Woo
YW
D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D011951:Receptors, Complement / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; D011994:Recombinant Proteins; D051193:Toll-Like Receptors; C032402:complement 1q receptor