PMID- 10414464
OWN - NLM
STAT- MEDLINE
DCOM- 19990729
LR  - 20240426
IS  - 0340-7004 (Print)
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Linking)
VI  - 48
IP  - 2-3
DP  - 1999 May-Jun
TI  - Simultaneous exposure to interleukin-18 and interleukin-10 in vitro 
      synergistically augments murine spleen natural killer cell activity.
PG  - 109-17
AB  - Interleukin-18 (IL-18) enhances interferon gamma (IFNgamma) production and 
      natural killer (NK) cell activity, and elicits protective antitumor effects in 
      vivo. IL-18 and IL-12 synergistically augment IFNgamma production reportedly 
      because IL-12 enhances IL-18 receptor (IL-18R) expression. We now show that IL-18 
      also synergizes with IL-10 to augment murine splenic NK activity against Yac-1 
      cells in a standard 4-h chromium-release assay, but IFNgamma production is only 
      slightly enhanced. This pattern of NK activity was also observed with severe 
      combined immunodeficient (SCID) mouse spleen cells indicating that the cytokines 
      were not acting on T or B cells. The cytokines had no priming activity on the 
      spleen cells and, when cells were left unstimulated for 24 h in culture, little 
      NK activity was induced when IL-18 was added for the next 24 h. The reverse 
      transcriptase/polymerase chain reaction revealed that IL-18 receptor (IL-18R) 
      mRNA was expressed early during in vitro spleen cell culture but none was 
      expressed after culture for 24 h regardless of the stimulus. Binding of 
      125I-labeled IL-18 revealed that exposure to IL-10 only slightly increased IL-18R 
      expression. Expression of perforin mRNA was constitutive and was unaffected by 
      the cytokines; however, Fas ligand (FasL) mRNA expression was strong in cultures 
      with IL-18 alone or combined with IL-10. When Fas-expressing cells and their 
      parental cells were used as targets, weak Fas-mediated cytolytic activity was 
      observed after exposure to IL-18, and this was further enhanced by combination 
      with IL-10. Finally, the augmentation of NK activity was abrogated by the 
      inhibitor concanamycin A, indicating that the enhanced NK activity is 
      perforin-dependent.
FAU - Micallef, M J
AU  - Micallef MJ
AD  - Fujisaki Institute, Hayashibara Biochemical Laboratories, Okayama, Japan.
FAU - Tanimoto, T
AU  - Tanimoto T
FAU - Torigoe, K
AU  - Torigoe K
FAU - Nishida, Y
AU  - Nishida Y
FAU - Kohno, K
AU  - Kohno K
FAU - Ikegami, H
AU  - Ikegami H
FAU - Kurimoto, M
AU  - Kurimoto M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Il18r1 protein, mouse)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-18 Receptor alpha Subunit)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Pore Forming Cytotoxic Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-18)
RN  - 0 (fas Receptor)
RN  - 126465-35-8 (Perforin)
RN  - 130068-27-8 (Interleukin-10)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Cytotoxicity, Immunologic
MH  - Drug Synergism
MH  - Female
MH  - Interferon-gamma/biosynthesis
MH  - Interleukin-10/*pharmacology
MH  - Interleukin-18/*pharmacology
MH  - Interleukin-18 Receptor alpha Subunit
MH  - Killer Cells, Natural/*drug effects/immunology
MH  - Lymphocyte Activation/drug effects
MH  - Membrane Glycoproteins/genetics
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Perforin
MH  - Pore Forming Cytotoxic Proteins
MH  - RNA, Messenger/analysis
MH  - Receptors, Interleukin/analysis
MH  - Receptors, Interleukin-18
MH  - Spleen/*drug effects/immunology
MH  - fas Receptor/genetics
PMC - PMC11037183
EDAT- 1999/07/22 00:00
MHDA- 1999/07/22 00:01
PMCR- 1999/06/01
CRDT- 1999/07/22 00:00
PHST- 1999/07/22 00:00 [pubmed]
PHST- 1999/07/22 00:01 [medline]
PHST- 1999/07/22 00:00 [entrez]
PHST- 1999/06/01 00:00 [pmc-release]
AID - 90480109.262 [pii]
AID - 10.1007/s002620050554 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 1999 May-Jun;48(2-3):109-17. doi: 
      10.1007/s002620050554.