Sensitivity Difference to the Suppressive Effect of Prostaglandin E2 Among Mouse Strains: A Possible Mechanism to Polarize Th2 Type Response in BALB/c Mice

• Published in: The Journal of immunology (1950) Vol. 164; no. 5; pp. 2386 - 2395
• Main Authors: Kuroda, Etsushi, Sugiura, Tsutomu, Zeki, Kazuya, Yoshida, Yasuhiro, Yamashita, Uki
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-03-2000
• Subjects: Adjuvants, Immunologic - administration & dosage; AIDS/HIV; Animals; Antigen-Presenting Cells - immunology; Binding Sites - immunology; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cells, Cultured; Cyclooxygenase 2; Cytokines - physiology; Dinoprostone - administration & dosage; Dinoprostone - metabolism; Dinoprostone - pharmacology; Immunity, Cellular - drug effects; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacology; Injections, Intramuscular; Injections, Intraperitoneal; Interferon-gamma - antagonists & inhibitors; Interferon-gamma - biosynthesis; Interleukin-10 - pharmacology; Isoenzymes - pharmacology; Male; Mice; Mice, Inbred BALB C - immunology; Mice, Inbred C3H; Mice, Inbred C57BL; Nitric Oxide - physiology; Nitrobenzenes - administration & dosage; Prostaglandin-Endoperoxide Synthases - pharmacology; Spleen - cytology; Spleen - drug effects; Spleen - immunology; Spleen - metabolism; Sulfonamides - administration & dosage; Th1 Cells - cytology; Th1 Cells - drug effects; Th1 Cells - enzymology; Th2 Cells - drug effects; Th2 Cells - immunology; Th2 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.5.2386

PGE2 has been shown to play a prominent role in regulating Th1 and Th2 type responses. We studied the role of PGE2 in IFN-gamma production by Staphylococcus aureus Cowan I-stimulated spleen cells from several mouse strains such as BALB/c, C3H/HeN, and C57BL/6. When spleen cells were pretreated with indomethacin (cyclooxygenase (COX)-1 and COX-2 inhibitor) or NS-398 (COX-2-specific inhibitor), S. aureus Cowan I -induced IFN-gamma production was increased more markedly in spleen cells from BALB/c mice than from C3H/HeN and C57BL/6 mouse. However, PGE2 production was not significantly different among spleen cells from three mouse strains. When various concentrations of PGE2 were exogeneously added to spleen cells, PGE2 showed a stronger suppressive effect on IFN-gamma production in spleen cells from BALB/c mice than from other strains of mice. This suppressive effect of PGE2 in BALB/c mice mainly depended on IL-12p70 production by APCs. More PGE2 binding sites were found in BALB/c spleen cells than in C3H/HeN spleen cells, indicating that the sensitivity difference to the suppressive effect of PGE2 was due to the difference of the number of PGE2 receptors. The administration of NS-398 into BALB/c mice enhanced Ag-specific IFN-gamma production, but not IL-4 production. This effect is the same as IL-12 administration in vivo. From these results, we propose that the modulation of PGE2 is important for Th1 activation via IFN-gamma and IL-12p70 production in vitro and in vivo and that PGE2 is one of the pivotal factors in the Th2-dominant immune response in BALB/c mice.