PMID- 18652873
OWN - NLM
STAT- MEDLINE
DCOM- 20081106
LR  - 20201209
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 250
IP  - 2-3
DP  - 2008 Sep 4
TI  - Intracellular expression of cytokines and granzyme B in auricular lymph nodes 
      draining skin exposed to irritants and sensitizers.
PG  - 116-23
LID - 10.1016/j.tox.2008.06.011 [doi]
AB  - The murine local lymph node assay (LLNA) has been extensively utilized to 
      evaluate sensitizing chemicals. However, there have been some concerns that its 
      use to discriminate between classes of chemicals is minimal. It is thus desirable 
      to identify better or alternative immune endpoints with in LLNA itself. Here, we 
      evaluated the protein and/or mRNA levels of cytokines and granzyme B (GzmB), a 
      cytotoxic lymphocyte product, to discriminate between sensitizers and irritants 
      and to characterize the chemical sensitizers when used as supplemental indicators 
      in LLNA endpoints. For this, CBA/N mice were topically treated daily with a 
      well-known chemical sensitizer such as a strong contact sensitizer 
      1-chloro-2,4-dinitrobenzene (DNCB), a skin contact sensitizer 
      2-phenyl-4-ethoxymethylene-5-oxazolone (OXA), and a skin or respiratory 
      sensitizer toluene 2,4-diisocyanate (TDI), and the non-sensitizing irritants, 
      croton oil (CRO) and nonanoic acid (NA), for 3 consecutive days. The protein 
      and/or mRNA levels in auricular lymph nodes draining the ear skin were then 
      analyzed by real-time RT-PCR and immunoassay. The sensitizers, but not the 
      irritants, evoked pronounced interleukin (IL)-2, IL-3 and IL-4 or interferon 
      (IFN)-gamma. Significantly, different sensitizers evoked different cytokine 
      patterns of IL-4 and IFN-gamma, as DNCB strongly up-regulated both IFN-gamma and 
      IL-4, OXA up-regulated IFN-gamma strongly but IL-4 weakly, and TDI up-regulated 
      IL-4 strongly but IFN-gamma weakly. The sensitizers also strongly up-regulated 
      GzmB mRNA, while the irritants had a much weaker effect. Thus, these cytokines 
      and GzmB mRNA may be useful as additional endpoints for discriminating between 
      irritants and sensitizers or contact and respiratory sensitizers in the LLNA.
FAU - Ku, Hyun-Ok
AU  - Ku HO
AD  - Toxicology & Chemistry Division, National Veterinary Research and Quarantine 
      Service, Anyang 430-824, Republic of Korea.
FAU - Jeong, Sang-Hee
AU  - Jeong SH
FAU - Kang, Hwan-Goo
AU  - Kang HG
FAU - Pyo, Hyun-Mi
AU  - Pyo HM
FAU - Cho, Joon-Hyoung
AU  - Cho JH
FAU - Son, Seong-Wan
AU  - Son SW
FAU - Kim, Hye-Ryeong
AU  - Kim HR
FAU - Lee, Kwang-Jick
AU  - Lee KJ
FAU - Ryu, Doug-Young
AU  - Ryu DY
LA  - eng
PT  - Journal Article
DEP - 20080704
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Cytokines)
RN  - 0 (Dinitrochlorobenzene)
RN  - 0 (Irritants)
RN  - 17X7AFZ1GH (Toluene 2,4-Diisocyanate)
RN  - 50-56-6 (Oxytocin)
RN  - 63231-63-0 (RNA)
RN  - 65907-78-0 (oxytocin, Asp(5)-)
RN  - EC 3.4.21.- (Granzymes)
SB  - IM
MH  - Animals
MH  - Cytokines/*biosynthesis
MH  - Dermatitis, Allergic Contact/*diagnosis
MH  - Dermatitis, Contact/*diagnosis
MH  - Diagnosis, Differential
MH  - Dinitrochlorobenzene/toxicity
MH  - Ear Auricle/drug effects/*metabolism
MH  - Female
MH  - Granzymes/*biosynthesis
MH  - Immunoassay
MH  - Irritants/*toxicity
MH  - *Local Lymph Node Assay
MH  - Lymph Nodes/drug effects/*metabolism
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Oxytocin/analogs & derivatives/toxicity
MH  - RNA/biosynthesis/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Skin Physiological Phenomena/*drug effects
MH  - Toluene 2,4-Diisocyanate/toxicity
EDAT- 2008/07/26 09:00
MHDA- 2008/11/07 09:00
CRDT- 2008/07/26 09:00
PHST- 2008/04/30 00:00 [received]
PHST- 2008/06/24 00:00 [revised]
PHST- 2008/06/24 00:00 [accepted]
PHST- 2008/07/26 09:00 [pubmed]
PHST- 2008/11/07 09:00 [medline]
PHST- 2008/07/26 09:00 [entrez]
AID - S0300-483X(08)00273-4 [pii]
AID - 10.1016/j.tox.2008.06.011 [doi]
PST - ppublish
SO  - Toxicology. 2008 Sep 4;250(2-3):116-23. doi: 10.1016/j.tox.2008.06.011. Epub 2008 
      Jul 4.