PMID- 19289819
OWN - NLM
STAT- MEDLINE
DCOM- 20090506
LR  - 20240109
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 106
IP  - 14
DP  - 2009 Apr 7
TI  - Prostaglandin mediates IL-23/IL-17-induced neutrophil migration in inflammation 
      by inhibiting IL-12 and IFNgamma production.
PG  - 5954-9
LID - 10.1073/pnas.0812782106 [doi]
AB  - IL-23/IL-17-induced neutrophil recruitment plays a pivotal role in rheumatoid 
      arthritis (RA). However, the mechanism of the neutrophil recruitment is obscure. 
      Here we report that prostaglandin enhances the IL-23/IL-17-induced neutrophil 
      migration in a murine model of RA by inhibiting IL-12 and IFN gamma production. 
      Methylated BSA (mBSA) and IL-23-induced neutrophil migration was inhibited by 
      anti-IL-23 and anti-IL-17 antibodies, COX inhibitors, IL-12, or IFNgamma but was 
      enhanced by prostaglandin E(2) (PGE(2)). IL-23-induced IL-17 production was 
      increased by PGE(2) and suppressed by COX-inhibition or IL-12. Furthermore, COX 
      inhibition failed to reduce IL-23-induced neutrophil migration in IL-12- or 
      IFNgamma-deficient mice. IL-17-induced neutrophil migration was not affected by 
      COX inhibitors, IL-12, or IFNgamma but was inhibited by MK886 (a leukotriene 
      synthesis inhibitor), anti-TNFalpha, anti-CXCL1, and anti-CXCL5 antibodies and by 
      repertaxin (a CXCR1/2 antagonist). These treatments all inhibited mBSA- or 
      IL-23-induced neutrophil migration. IL-17 induced neutrophil chemotaxis through a 
      CXC chemokines-dependent pathway. Our results suggest that prostaglandin plays an 
      important role in IL-23-induced neutrophil migration in arthritis by enhancing 
      IL-17 synthesis and by inhibiting IL-12 and IFNgamma production. We thus provide 
      a mechanism for the pathogenic role of the IL-23/IL-17 axis in RA and also 
      suggest an additional mechanism of action for nonsteroidal anti-inflammatory 
      drugs.
FAU - Lemos, Henrique P
AU  - Lemos HP
AD  - Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of 
      Sao Paulo, Sao Paulo 14.049-900, Brazil.
FAU - Grespan, Renata
AU  - Grespan R
FAU - Vieira, Silvio M
AU  - Vieira SM
FAU - Cunha, Thiago M
AU  - Cunha TM
FAU - Verri, Waldiceu A Jr
AU  - Verri WA Jr
FAU - Fernandes, Karla S S
AU  - Fernandes KS
FAU - Souto, Fabricio O
AU  - Souto FO
FAU - McInnes, Iain B
AU  - McInnes IB
FAU - Ferreira, Sergio H
AU  - Ferreira SH
FAU - Liew, Foo Y
AU  - Liew FY
FAU - Cunha, Fernando Q
AU  - Cunha FQ
LA  - eng
GR  - G0801198/MRC_/Medical Research Council/United Kingdom
GR  - G9818261/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090316
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukin-23)
RN  - 0 (Prostaglandins)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Arthritis, Rheumatoid/*pathology
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - Dinoprostone/pharmacology
MH  - Inflammation/*metabolism
MH  - Interferon-gamma/*antagonists & inhibitors
MH  - Interleukin-12/*antagonists & inhibitors
MH  - Interleukin-17/biosynthesis/*immunology
MH  - Interleukin-23/*immunology
MH  - Mice
MH  - Neutrophil Infiltration/*immunology
MH  - Prostaglandins/*physiology
PMC - PMC2667068
COIS- The authors declare no conflict of interest.
EDAT- 2009/03/18 09:00
MHDA- 2009/05/07 09:00
PMCR- 2009/10/07
CRDT- 2009/03/18 09:00
PHST- 2009/03/18 09:00 [entrez]
PHST- 2009/03/18 09:00 [pubmed]
PHST- 2009/05/07 09:00 [medline]
PHST- 2009/10/07 00:00 [pmc-release]
AID - 0812782106 [pii]
AID - 6609 [pii]
AID - 10.1073/pnas.0812782106 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5954-9. doi: 
      10.1073/pnas.0812782106. Epub 2009 Mar 16.