PMID- 18780764
OWN - NLM
STAT- MEDLINE
DCOM- 20090210
LR  - 20120215
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 23
IP  - 1
DP  - 2009 Jan
TI  - Autocrine role of endogenous interleukin-18 on inflammatory cytokine generation 
      by human neutrophils.
PG  - 194-203
LID - 10.1096/fj.08-110213 [doi]
AB  - Neutrophils are key players of innate immunity and influence inflammatory and 
      immune reactions through the production of numerous cytokines. Interleukin-18 
      (IL-18) is known to stimulate several neutrophil responses, and recent evidence 
      suggests that neutrophils might represent a source of IL-18. Here, we show that 
      neutrophils constitutively produce both IL-18 and its antagonist, IL-18BP. Cell 
      activation does not affect IL-18BP release but leads to an increased gene 
      expression and secretion of IL-18, a process that depends on NF-kappaB 
      activation. Moreover, endogenous IL-18 feeds back on the neutrophils to augment 
      cytokine generation in lipopolysaccharide-treated cells. Accordingly, exogenous 
      IL-18 can induce the gene expression and release of several inflammatory 
      cytokines in neutrophils, including its own expression. We finally report that 
      IL-18 activates the p38 MAPK, MEK/ERK, and PI3K/Akt pathways in neutrophils. The 
      IKK cascade is also activated by IL-18, resulting in IkappaB-alpha degradation, 
      NF-kappaB activation, and RelA phosphorylation. Accordingly, these pathways 
      contribute to the generation of inflammatory cytokines in IL-18-stimulated 
      neutrophils. By contrast, the phosphorylation and DNA-binding activity of various 
      STAT proteins were not induced by IL-18. Collectively, our results unveil new 
      interactions between IL-18 and neutrophils and further support a role for these 
      cells in influencing both innate and adaptive immunity.
FAU - Fortin, Carl F
AU  - Fortin CF
AD  - Pulmonary Division, Faculty of Medicine, Universite de Sherbrooke, Sherbrooke, 
      QC, Canada J1H 5N4.
FAU - Ear, Thornin
AU  - Ear T
FAU - McDonald, Patrick P
AU  - McDonald PP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080909
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-18)
RN  - 0 (NF-kappa B)
RN  - 0 (interleukin-18 binding protein)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Gene Expression Regulation/physiology
MH  - Humans
MH  - I-kappa B Kinase/metabolism
MH  - Inflammation/*metabolism
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Interleukin-18/*metabolism
MH  - NF-kappa B/metabolism
MH  - Neutrophils/*metabolism
MH  - Oncogene Protein v-akt/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Signal Transduction
MH  - Time Factors
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2008/09/11 09:00
MHDA- 2009/02/12 09:00
CRDT- 2008/09/11 09:00
PHST- 2008/09/11 09:00 [pubmed]
PHST- 2009/02/12 09:00 [medline]
PHST- 2008/09/11 09:00 [entrez]
AID - fj.08-110213 [pii]
AID - 10.1096/fj.08-110213 [doi]
PST - ppublish
SO  - FASEB J. 2009 Jan;23(1):194-203. doi: 10.1096/fj.08-110213. Epub 2008 Sep 9.