PMID- 17258468
OWN - NLM
STAT- MEDLINE
DCOM- 20070608
LR  - 20091119
IS  - 1043-4666 (Print)
IS  - 1043-4666 (Linking)
VI  - 36
IP  - 5-6
DP  - 2006 Dec
TI  - STAT1 and STAT3 phosphorylation by porins are independent of JAKs but are 
      dependent on MAPK pathway and plays a role in U937 cells production of 
      interleukin-6.
PG  - 218-28
AB  - A group of transcription factors, termed signal transducers and activators of 
      transcription (STATs), appears to orchestrate the downstream events propagated by 
      cytokine/growth factor interactions with their cognate receptors. Similarly, 
      cytoplasmic Janus kinases (JAKs) seem to play a critical role in diverse signal 
      transduction pathways that govern cellular survival, proliferation, 
      differentiation and apoptosis. In this work, we analysed the effects of the 
      Salmonella enterica serovar Typhimurium porins on signaling by the JAK/STAT 
      pathway and IL-6 release in U937 cells. Porins and LPS of membrane from 
      Gram-negative bacteria are factors implicated in septic shock. In our assays 
      porins induce interleukin-6 (IL-6) release (110+/-2.6pg/ml) 24h after stimulation 
      and STAT1/STAT3 tyrosine (Tyr701/Tyr705) and serine (Ser727) phosphorylation 
      after 15min. By using several selective inhibitors we demonstrate that porins 
      modulate the activation of STAT1/STAT3 through mitogen activated protein kinases 
      (MAPKs) and not JAKs. Furthermore, we demonstrated that STAT1 and STAT3 are not 
      involved in the modulation of IL-6 release in U937 cells stimulated with porins. 
      Inhibition of tyrosine/serine phosphorylation mediated by MAPKs of STAT1 and 
      STAT3 decrease the IL-6 secretion following porin stimulation. Therefore, 
      suggesting a key role of this pathway in phosphorylation of Ser 727 in STAT1 and 
      STAT3. These results are confirmed by porin or LPS-induced nuclear translocation 
      of STAT1 and STAT3 in U937 cells.
FAU - Galdiero, Marilena
AU  - Galdiero M
AD  - Department of Experimental Medicine, Section of Microbiology and Clinical 
      Microbiology, Faculty of Medicine, Second University of Naples, Naples, Italy.
FAU - Vitiello, Mariateresa
AU  - Vitiello M
FAU - D'Isanto, Marina
AU  - D'Isanto M
FAU - Raieta, Katia
AU  - Raieta K
FAU - Galdiero, Emilia
AU  - Galdiero E
LA  - eng
PT  - Journal Article
DEP - 20070126
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Porins)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - EC 2.7.10.2 (Janus Kinases)
SB  - IM
MH  - Humans
MH  - Interleukin-6/*metabolism
MH  - Janus Kinases/metabolism
MH  - *MAP Kinase Signaling System
MH  - Monocytes/immunology/*metabolism
MH  - Phosphorylation
MH  - Porins/*metabolism
MH  - STAT1 Transcription Factor/antagonists & inhibitors/*metabolism
MH  - STAT3 Transcription Factor/antagonists & inhibitors/*metabolism
MH  - U937 Cells
EDAT- 2007/01/30 09:00
MHDA- 2007/06/09 09:00
CRDT- 2007/01/30 09:00
PHST- 2006/09/26 00:00 [received]
PHST- 2006/11/28 00:00 [revised]
PHST- 2006/12/16 00:00 [accepted]
PHST- 2007/01/30 09:00 [pubmed]
PHST- 2007/06/09 09:00 [medline]
PHST- 2007/01/30 09:00 [entrez]
AID - S1043-4666(06)00345-0 [pii]
AID - 10.1016/j.cyto.2006.12.003 [doi]
PST - ppublish
SO  - Cytokine. 2006 Dec;36(5-6):218-28. doi: 10.1016/j.cyto.2006.12.003. Epub 2007 Jan 
      26.