Chemokine production and adhesion molecule expression by neural cells exposed to IL-1, TNF alpha and interferon gamma.
We investigated the effect of TNF alpha, IL-1alpha and IFN gamma on two neuroblastoma (NB) cell lines (SK-N-SH and SK-N-MC). These lines responded differentially to IL-1alpha, TNF alpha and IFN gamma for MCP-1 and IL-8 production and expression of the ICAM-1 and VCAM-1 adhesion molecules. None of the cytokines induced MCP-1 or IL-8 on SK-N-MC cells. Both chemokines were produced in response to IL-1alpha by SK-N-SH cells, while TNF alpha induced mainly MCP-1 production. Addition of IFN gamma decreased IL-8, but not MCP-1 production. These responses correlated with monocyte and neutrophil chemotactic activity in NB culture supernatants. This activity was neutralized by antibodies to IL-8 and MCP-1. The expression of ICAM-1 on SK-N-MC was up-regulated by TNF alpha or IFN gamma, while IL-1alpha also upregulated ICAM-1 on SK-N-SH cells. VCAM-1 expression on SK-N-SH was induced by IL-1alpha and TNF alpha and IFN gamma synergized with TNF alpha in this respect on both NB cell lines. These results suggest that mechanisms for chemokine production and VCAM-1 and ICAM-1 upregulation by inflammatory cytokines differ and IFN gamma, in conjunction with TNF alpha, stimulate neural cell responses (high MCP-1 and VCAM-1 and decreased IL-8) favouring mononuclear cell recruitment.
Chuluyan
H E
HE
Department of Pediatrics, Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
Lang
B J
BJ
Yoshimura
T
T
Kenney
J S
JS
Issekutz
A C
AC
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D018925:Chemokines; D019012:Integrin beta1; D007375:Interleukin-1; D016209:Interleukin-8; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma