PMID- 12442334
OWN - NLM
STAT- MEDLINE
DCOM- 20030130
LR  - 20180815
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 32
IP  - 12
DP  - 2002 Dec
TI  - CCL20/macrophage inflammatory protein-3alpha production in LPS-stimulated 
      neutrophils is enhanced by the chemoattractant 
      formyl-methionyl-leucyl-phenylalanine and IFN-gamma through independent 
      mechanisms.
PG  - 3515-24
AB  - We have recently demonstrated that polymorphonuclear neutrophils (PMN), when 
      cultured with LPS or TNF-alpha, have the capacity to release CCL20, a chemokine 
      primarily chemotactic for immature dendritic cells and specific lymphocyte 
      subsets. Here, we report that the chemoattractant 
      formyl-methionyl-leucyl-phenylalanine (fMLP), as well as the immunoregulatory 
      cytokine IFN-gamma, can significantly up-modulate the production of 
      neutrophil-derived CCL20 through entirely unrelated mechanisms. We found that 
      fMLP dramatically up-regulates CCL20 mRNA expression and synthesis in neutrophils 
      stimulated with LPS for 2-3 h, and that its effect takes place through CCL20 mRNA 
      stabilization. In contrast, IFN-gamma potentiates CCL20 gene expression and 
      production only after 21 h of LPS treatment, its effect being mediated by 
      endogenous TNF-alpha in an autocrine fashion, as revealed using neutralizing 
      anti-TNF-alpha antibodies added to IFN-gamma plus LPS-treated PMN. Finally, we 
      demonstrate that activation of p38 mitogen-activated protein kinase (MAPK) plays 
      an important role in mediating the production of CCL20 induced by LPS (with or 
      without IFN-gamma), whereas activation of p42/44 extracellular signal-regulated 
      kinases (ERK) is involved in the enhancing effect of fMLP. Taken together, these 
      findings identify novel biological actions exerted by fMLP and IFN-gamma, 
      potentially involved in the orchestration of inflammatory and immune responses 
      within epithelial and mucosal tissue.
FAU - Scapini, Patrizia
AU  - Scapini P
AD  - Department of Pathology, Section of General Pathology, University of Verona, 
      Verona, Italy.
FAU - Crepaldi, Luca
AU  - Crepaldi L
FAU - Pinardi, Cristina
AU  - Pinardi C
FAU - Calzetti, Federica
AU  - Calzetti F
FAU - Cassatella, Marco A
AU  - Cassatella MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (CCL20 protein, human)
RN  - 0 (CCR6 protein, human)
RN  - 0 (Chemokine CCL20)
RN  - 0 (Chemokines, CC)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Imidazoles)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR6)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Recombinant Proteins)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Chemokine CCL20
MH  - Chemokines, CC/*biosynthesis/genetics
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - In Vitro Techniques
MH  - Interferon-gamma/*pharmacology
MH  - Lipopolysaccharides/*pharmacology
MH  - Macrophage Inflammatory Proteins/*biosynthesis/genetics
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors
MH  - N-Formylmethionine Leucyl-Phenylalanine/*pharmacology
MH  - Neutrophils/*drug effects/*immunology
MH  - Pyridines/pharmacology
MH  - RNA Stability/drug effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, CCR6
MH  - *Receptors, Chemokine
MH  - Recombinant Proteins
MH  - Signal Transduction/drug effects
MH  - Up-Regulation/drug effects
EDAT- 2002/11/21 04:00
MHDA- 2003/01/31 04:00
CRDT- 2002/11/21 04:00
PHST- 2002/11/21 04:00 [pubmed]
PHST- 2003/01/31 04:00 [medline]
PHST- 2002/11/21 04:00 [entrez]
AID - 10.1002/1521-4141(200212)32:12<3515::AID-IMMU3515>3.0.CO;2-3 [doi]
PST - ppublish
SO  - Eur J Immunol. 2002 Dec;32(12):3515-24. doi: 
      10.1002/1521-4141(200212)32:12<3515::AID-IMMU3515>3.0.CO;2-3.