PMID- 18250323
OWN - NLM
STAT- MEDLINE
DCOM- 20080313
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 105
IP  - 7
DP  - 2008 Feb 19
TI  - IL-33 mediates antigen-induced cutaneous and articular hypernociception in mice.
PG  - 2723-8
LID - 10.1073/pnas.0712116105 [doi]
AB  - IL-33, a new member of the IL-1 family, signals through its receptor ST2 and 
      induces T helper 2 (Th2) cytokine synthesis and mediates inflammatory response. 
      We have investigated the role of IL-33 in antigen-induced hypernociception. 
      Recombinant IL-33 induced cutaneous and articular mechanical hypernociception in 
      a time- and dose-dependent manner. The hypernociception was inhibited by soluble 
      (s) ST2 (a decoy receptor of IL-33), IL-1 receptor antagonist (IL-1ra), bosentan 
      [a dual endothelin (ET)(A)/ET(B) receptor antagonist], clazosentan (an ET(A) 
      receptor antagonist), or indomethacin (a cyclooxygenase inhibitor). IL-33 induced 
      hypernociception in IL-18(-/-) mice but not in TNFR1(-/-) or IFNgamma(-/-) mice. 
      The IL-33-induced hypernociception was not affected by blocking IL-15 or 
      sympathetic amines (guanethidine). Furthermore, methylated BSA (mBSA)-induced 
      cutaneous and articular mechanical hypernociception depended on TNFR1 and 
      IFNgamma and was blocked by sST2, IL-1ra, bosentan, clazosentan, and 
      indomethacin. mBSA also induced significant IL-33 and ST2 mRNA expression. 
      Importantly, we showed that mBSA induced hypernociception via the IL-33 --> 
      TNFalpha --> IL-1beta --> IFNgamma --> ET-1 --> PGE(2) signaling cascade. These 
      results therefore demonstrate that IL-33 is a key mediator of immune inflammatory 
      hypernociception normally associated with a Th1 type of response, revealing a 
      hitherto unrecognized function of IL-33 in a key immune pharmacological pathway 
      that may be amenable to therapeutic intervention.
FAU - Verri, Waldiceu A Jr
AU  - Verri WA Jr
AD  - Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of 
      Sao Paulo, Av. Bandeirantes, 3900, 14049-900-Ribeirao Preto, Sao Paulo, Brazil.
FAU - Guerrero, Ana T G
AU  - Guerrero AT
FAU - Fukada, Sandra Y
AU  - Fukada SY
FAU - Valerio, Daniel A
AU  - Valerio DA
FAU - Cunha, Thiago M
AU  - Cunha TM
FAU - Xu, Damo
AU  - Xu D
FAU - Ferreira, Sergio H
AU  - Ferreira SH
FAU - Liew, Foo Y
AU  - Liew FY
FAU - Cunha, Fernando Q
AU  - Cunha FQ
LA  - eng
GR  - G9818261/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080204
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 (Antigens)
RN  - 0 (Endothelin-1)
RN  - 0 (Interleukins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Serum Albumin)
RN  - 0 (aflatoxin B1-bovine serum albumin)
RN  - 9N2N2Y55MH (Aflatoxin B1)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Aflatoxin B1/pharmacology
MH  - Animals
MH  - Antigens/*immunology
MH  - Dinoprostone/biosynthesis
MH  - Endothelin-1/genetics
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Interleukins/*immunology
MH  - Male
MH  - Methylation
MH  - Mice
MH  - Mice, Knockout
MH  - Pain/chemically induced/*immunology/pathology
MH  - RNA, Messenger/genetics
MH  - Serum Albumin/pharmacology
MH  - Skin/blood supply/drug effects/*immunology/pathology
PMC - PMC2268203
COIS- The authors declare no conflict of interest.
EDAT- 2008/02/06 09:00
MHDA- 2008/03/14 09:00
PMCR- 2008/08/19
CRDT- 2008/02/06 09:00
PHST- 2008/02/06 09:00 [pubmed]
PHST- 2008/03/14 09:00 [medline]
PHST- 2008/02/06 09:00 [entrez]
PHST- 2008/08/19 00:00 [pmc-release]
AID - 0712116105 [pii]
AID - 9327 [pii]
AID - 10.1073/pnas.0712116105 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2723-8. doi: 
      10.1073/pnas.0712116105. Epub 2008 Feb 4.