Primary hepatocytes from mice treated with IL-2/IL-12 produce T cell chemoattractant activity that is dependent on monokine induced by IFN-gamma (Mig) and chemokine responsive to gamma-2 (Crg-2).
The IFN-gamma-inducible proteins monokine induced by IFN-gamma (Mig) and chemokine responsive to gamma-2 (Crg-2) can contribute to IL-12-induced antiangiogenic and leukocyte-recruiting activities, but the extent to which leukocytes vs parenchymal cells in different organs contribute to the production of these molecules remains unclear. The results presented herein show that IFN-gamma-dependent induction of Mig and Crg-2 gene expression can occur in many nonlymphoid organs, and these genes are rapidly induced in purified hepatocytes isolated from mice treated with IL-2 plus IL-12, or from Hepa 1-6 hepatoma cells treated in vitro with IFN-gamma. In addition to depending on IFN-gamma, the ability of IL-12 or IL-2/IL-12 to induce Mig and Crg-2 gene expression in purified hepatocytes also is accompanied by the coordinate up-regulation of the IFN-gamma R alpha and beta-chains, in the absence of IL-12R components. Supernatants of primary hepatocytes obtained from mice treated in vivo with IL-2/IL-12 or from hepatocytes treated in vitro with IFN-gamma contain increased chemotactic activity for enriched human and mouse CD3(+) T cells, as well as mouse DX5(+) NK cells. The hepatocyte-derived chemotactic activity for mouse T cells but not NK cells was ablated by Abs specific for Mig and Crg-2. These results suggest that parenchymal cells in some organs may contribute substantially to initiation and/or amplification of inflammatory or antitumor responses.
Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA. j303nih@dsmc.or.kr
J W
JW
Park
M E
ME
Gruys
K
K
McCormick
J K
JK
Lee
J
J
Subleski
J M
JM
Wigginton
R G
RG
Fenton
J M
JM
Wang
R H
RH
Wiltrout
D000818:Animals; D002469:Cell Separation; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D004338:Drug Combinations; D005786:Gene Expression Regulation / Q000276:immunology; D022781:Hepatocytes / Q000276:immunology* / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D018664:Interleukin-12 / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000033:anatomy & histology / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D015846:Monokines / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018121:Receptors, Cytokine / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse; C485969:Cxcl9 protein, mouse; D004338:Drug Combinations; D007376:Interleukin-2; D015846:Monokines; D018121:Receptors, Cytokine; D018664:Interleukin-12; D007371:Interferon-gamma