IL-10 mediates sigma 1 receptor-dependent suppression of antitumor immunity.
Sigma receptors are unique endoplasmic reticulum proteins that mediate signaling for a variety of drugs. We determined the effect of sigma(1) receptor agonists on immune responses in a syngeneic lung cancer model. Sigma(1) receptor agonists, including cocaine, up-regulated splenocyte IL-10 mRNA and protein production in vitro in a sigma receptor-dependent, pertussis toxin-sensitive manner. In vivo, sigma(1) receptor agonists promoted tumor growth and induced IL-10 at the tumor site. Increased tumor growth was prevented by administration of specific Abs to IL-10 or by administration of specific sigma(1) receptor antagonists. We report that sigma(1) receptor ligands, including cocaine, augment tumor growth through an IL-10 dependent mechanism.
Zhu
Li X
LX
University of California Los Angeles Lung Cancer Research Program, Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095-1690, USA.
Sharma
Sherven
S
Gardner
Brian
B
Escuadro
Brian
B
Atianzar
Kimberly
K
Tashkin
Donald P
DP
Dubinett
Steven M
SM
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D000276:Adjuvants, Immunologic / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003042:Cocaine / Q000008:administration & dosage / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D006131:Growth Inhibitors / Q000008:administration & dosage; D007121:Immunocompetence / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009025:Morpholines / Q000008:administration & dosage / Q000378:metabolism; D009368:Neoplasm Transplantation; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D000097605:Sigma-1 Receptor
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D003042:Cocaine; D016207:Cytokines; D006131:Growth Inhibitors; D007371:Interferon-gamma; D016753:Interleukin-10; D009025:Morpholines; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C071738:2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate