PMID- 25659093
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 2
DP  - 2015
TI  - Interferon regulatory factor (IRF)-1 is a master regulator of the cross talk 
      between macrophages and L929 fibrosarcoma cells for nitric oxide dependent 
      tumoricidal activity.
PG  - e0117782
LID - 10.1371/journal.pone.0117782 [doi]
LID - e0117782
AB  - Macrophage tumoricidal activity relies, mainly, on the release of Tumor Necrosis 
      Factor alpha (TNFalpha) and/or on reactive oxygen or nitrogen intermediates. In the 
      present work, we investigated the cytotoxic activity of resident peritoneal 
      macrophages against L929 fibrosarcoma cell line in vitro and in vivo. Resident 
      macrophages lysed L929 cells in a mechanism independent of TNFalpha and cell-to-cell 
      contact. The cytotoxic activity was largely dependent on nitric oxide (NO) 
      release since treatment with L-NAME (NOS inhibitor) inhibited L929 cells killing. 
      Macrophages from mice with targeted deletion of inducible NO synthase (iNOS) 
      together with L929 cells produced less NO and displayed lower, but still 
      significant, tumoricidal activity. Notably, NO production and tumor lysis were 
      abolished in co-cultures with macrophages deficient in Interferon Regulatory 
      Factor, IRF-1. Importantly, the in vitro findings were reproduced in vivo as 
      IRF-1 deficient animals inoculated i.p with L929 cells were extremely susceptible 
      to tumor growth and their macrophages did not produce NO, while WT mice killed 
      L929 tumor cells and their macrophages produced high levels of NO. Our results 
      indicate that IRF-1 is a master regulator of bi-directional interaction between 
      macrophages and tumor cells. Overall, IRF-1 was essential for NO production by 
      co-cultures and macrophage tumoricidal activity in vitro as well as for the 
      control of tumor growth in vivo.
FAU - Nascimento, Flavia R F
AU  - Nascimento FR
AD  - Department of Pathology, Center of Biological Sciences and Health, Federal 
      University of Maranhao, Sao Luis, Brazil.
FAU - Gomes, Eliane A
AU  - Gomes EA
AD  - Department of Imunology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
FAU - Russo, Momtchilo
AU  - Russo M
AD  - Department of Imunology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
FAU - Lepique, Ana P
AU  - Lepique AP
AD  - Department of Imunology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20150206
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Interferon Regulatory Factor-1)
RN  - 0 (Irf1 protein, mouse)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Animals
MH  - Cell Communication/*immunology
MH  - Cell Line, Tumor
MH  - Female
MH  - Fibrosarcoma/*immunology/pathology
MH  - Interferon Regulatory Factor-1/*immunology
MH  - Macrophages, Peritoneal/*immunology/pathology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Nitric Oxide/*immunology
PMC - PMC4449231
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/02/07 06:00
MHDA- 2015/02/07 06:01
PMCR- 2015/02/06
CRDT- 2015/02/07 06:00
PHST- 2014/10/20 00:00 [received]
PHST- 2015/01/01 00:00 [accepted]
PHST- 2015/02/07 06:00 [entrez]
PHST- 2015/02/07 06:00 [pubmed]
PHST- 2015/02/07 06:01 [medline]
PHST- 2015/02/06 00:00 [pmc-release]
AID - PONE-D-14-47107 [pii]
AID - 10.1371/journal.pone.0117782 [doi]
PST - epublish
SO  - PLoS One. 2015 Feb 6;10(2):e0117782. doi: 10.1371/journal.pone.0117782. 
      eCollection 2015.