PMID- 8381194
OWN - NLM
STAT- MEDLINE
DCOM- 19930301
LR  - 20131121
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 7
IP  - 2
DP  - 1993 Feb
TI  - Interleukin-2 enhances the production of tumor necrosis factor-alpha in activated 
      B-type chronic lymphocytic leukemia (B-CLL) cells.
PG  - 226-34
AB  - Tumor necrosis factor-alpha (TNF-alpha) has recently been implicated as a 
      regulator growth and differentiation of normal and malignant B cells. We utilized 
      a selected clone (I-83) of primary resting B-type chronic lymphocytic leukemia 
      (B-CLL) cells, inducible to activation, growth and differentiation in vitro, as a 
      model system to study the possible role of TNF-alpha as an autocrine growth 
      factor for such cells. Our results show that unstimulated I-83 B-CLL cells 
      produced a low level of TNF-alpha mRNA, as shown by Northern blot analysis, and 
      cytoplasmic TNF-alpha, determined in individual cells by immunocytochemistry. 
      Secreted TNF-alpha could, however, not be detected in the medium by ELISA. 
      TNF-alpha synthesis and secretion was, however, induced to high levels by 
      stimulation of the B-CLL cells with interleukin-2 (IL-2) after activation by 
      12-O-tetradecanoylphorbol-13-acetate (TPA) or Staphylococcus aureus Cowan strain 
      I (SAC) and B-cell stimulatory factor-MP6 (thioredoxin). A moderate increase in 
      TNF-alpha secretion was also induced by TPA or IL-2 alone. IL-4 did not have any 
      major effects on the production of TNF-alpha in activated cells, but inhibited 
      the IL-2-induced production of TNF-alpha in SAC-activated cells. The cell surface 
      expression of TNF-alpha receptors (TNF-R), as determined by binding assay using 
      125I-labelled recombinant TNF-alpha (rTNF-alpha), was also induced after SAC or 
      TPA activation, but shed receptors (TNF-binding proteins) were only observed 
      after TPA activation. Exogenously added rTNF-alpha in combination with TPA or SAC 
      induced a high level of DNA synthesis in I-83 B-CLL cells. The increased 
      endogenous production and secretion of TNF-alpha during induced growth 
      stimulation, the induced expression of TNF-R, and the mitogenic effect of 
      TNF-alpha on activated B-CLL cells raise the question whether TNF-alpha may 
      function as an autocrine co-stimulator of B-CLL cell growth as recently 
      suggested. anti-TNF-alpha and anti-TNF-R antibodies, however, failed to inhibit 
      the IL-2- and IL-4-induced proliferation of activated I-83 B-CLL cells.
FAU - Larsson, L G
AU  - Larsson LG
AD  - Department of Pathology, University of Uppsala, University Hospital, Sweden.
FAU - Carlsson, M
AU  - Carlsson M
FAU - Schena, M
AU  - Schena M
FAU - Lantz, M
AU  - Lantz M
FAU - Caligaris-Cappio, F
AU  - Caligaris-Cappio F
FAU - Nilsson, K
AU  - Nilsson K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Interleukin-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 207137-56-2 (Interleukin-4)
RN  - 52500-60-4 (Thioredoxins)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - DNA, Neoplasm/biosynthesis
MH  - Humans
MH  - Interleukin-2/*pharmacology
MH  - Interleukin-4/pharmacology
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*metabolism
MH  - RNA, Messenger/*biosynthesis
MH  - Receptors, Cell Surface/*metabolism
MH  - Receptors, Tumor Necrosis Factor
MH  - Staphylococcus aureus
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Thioredoxins/pharmacology
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/genetics
EDAT- 1993/02/01 00:00
MHDA- 1993/02/01 00:01
CRDT- 1993/02/01 00:00
PHST- 1993/02/01 00:00 [pubmed]
PHST- 1993/02/01 00:01 [medline]
PHST- 1993/02/01 00:00 [entrez]
PST - ppublish
SO  - Leukemia. 1993 Feb;7(2):226-34.