IL-12 and IL-18 induce MAP kinase-dependent adhesion of T cells to extracellular matrix components.
Cytokines and chemokines play an essential role in recruiting leukocytes from the circulation to the peripheral sites of inflammation by modulating cellular interactions with endothelial cell ligands and extracellular matrix (ECM). Herein, we examined regulation of T cell adhesion to ECM ligands by two major proinflammatory cytokines, interleukin (IL)-12 and IL-18. IL-12 and IL-18 induced T cell adhesion to fibronectin (FN) and hyaluronic acid at low (pM) concentrations that were mediated by specific adhesion molecules expressed on the T cell surface, namely, beta(1) integrins and CD44, respectively. The induction of adhesion by IL-12 and IL-18 was inhibited by extracellular signal-regulated kinase and p38 mitogen-activated protein kinase inhibitors (PD098059 and SB203580, respectively). In contrast, IL-12- and IL-18-induced interferon-gamma (INF-gamma) secretion from T cells was inhibited by SB203580, but not by PD098059. It is interesting that low concentrations of IL-12 and IL-18 induced T cell adhesion to FN in a synergistic manner. Thus, in addition to the regulation of late inflammatory functions such as INF-gamma production, IL-12 and IL-18, alone or in combination, regulate early inflammatory events such as T cell adhesion to inflamed sites.
Ariel
Amiram
A
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Novick
Daniela
D
Rubinstein
Menachem
M
Dinarello
Charles A
CA
Lider
Ofer
O
Hershkoviz
Rami
R
D002448:Cell Adhesion; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology; D006820:Hyaluronic Acid / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D019012:Integrin beta1 / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D020382:Interleukin-18 / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D005419:Flavonoids; D018960:Hyaluronan Receptors; D007093:Imidazoles; D019012:Integrin beta1; D020382:Interleukin-18; D011725:Pyridines; D018664:Interleukin-12; D007371:Interferon-gamma; D006820:Hyaluronic Acid; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one