Stanniocalcin-1, an inhibitor of macrophage chemotaxis and chemokinesis.
In macrophages, changes in intracellular calcium have been associated with activation of cellular processes that regulate cell adhesion and motility and are important for the response of macrophages to antigenic stimuli. The mammalian counterpart of the fish calcium-regulating hormone stanniocalcin-1 (STC1) is expressed in multiple organs including the thymus and spleen, and hence, we hypothesized that it may have a role in modulating the immune/inflammatory response. Using murine macrophage-like (RAW264.7) and human monoblast-like (U937) cells to study chemotaxis in vitro, we found that STC1 attenuated chemokinesis and diminished the chemotactic response to monocyte chemotactic protein-1 (MCP-1) and stromal cell-derived factor-1alpha. Consistent with these findings, STC1 blunted the rise in intracellular calcium following MCP-1 stimulation in RAW264.7 cells. In vivo studies suggested differential expression of STC1 in obstructed kidney and localization to macrophages. MCP-1 and STC1 transcripts were both upregulated following ureteric obstruction, suggesting a functional association between the two genes. Our data suggest a role for mammalian STC1 in modulating the immune/inflammatory response.
Renal Section, Deptartment of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
John
J
Kanellis
Roger
R
Bick
Gabriela
G
Garcia
Luan
L
Truong
Chun Chui
CC
Tsao
Dariush
D
Etemadmoghadam
Brian
B
Poindexter
Lili
L
Feng
Richard J
RJ
Johnson
David
D
Sheikh-Hamad
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020298:U937 Cells; D015854:Up-Regulation; D014517:Ureteral Obstruction / Q000276:immunology* / Q000503:physiopathology
D018932:Chemokine CCL2; D006023:Glycoproteins; D012333:RNA, Messenger; C051795:teleocalcin; D002118:Calcium