PMID- 23621293
OWN - NLM
STAT- MEDLINE
DCOM- 20140211
LR  - 20130628
IS  - 1460-2202 (Electronic)
IS  - 0271-3683 (Linking)
VI  - 38
IP  - 8
DP  - 2013 Aug
TI  - Involvement of NFkappaB in the production of chemokines by rat and human conjunctival 
      cells cultured under allergenic conditions.
PG  - 825-34
LID - 10.3109/02713683.2013.780623 [doi]
AB  - PURPOSE: The purpose of present studies was to determine the involvement of NFkappaB 
      and STAT6 transcription factors in the production of cytokines by the fibroblasts 
      and epithelial cells in conjunctiva. METHODS: An in vitro model of allergic 
      conjunctivitis was developed by sensitizing and challenging rat mast cells with 
      anti-dinitrophenyl (DNP) IgE and DNP-BSA, and then using the conditioned medium 
      to stimulate rat conjunctival fibroblasts. Chemokines (eotaxin-1, IL-8, and 
      RANTES -- Regulated and Normal T cell Expressed and Secreted) released from cells 
      into the medium was determined by ELISA. Human conjunctival fibroblasts and 
      epithelial cells were also directly stimulated with exogenous cytokines tumor 
      necrosis factor (TNF)-alpha or IL-4. Degradation of IkappaB-alpha and phosphorylation of 
      STAT6 were assessed by immunoblotting. For inhibition of NFkappaB or STAT6 
      activation, upstream regulators IkappaB kinase and Janus protein tyrosine kinases 
      (JAK) were inhibited by use of BMS-345541 and JAK inhibitor 1. An in vivo model 
      of conjunctivitis was also produced in rats by intraperitoneal injection of 
      ovalbumin (OA) with aluminum hydroxide and challenge at 21 d with OA eye drops. 
      RESULTS: Stimulated rat mast cells released TNF-alpha and IL-4. TNF-alpha induced NFkappaB 
      activation in rat and human conjunctival fibroblasts and epithelial cells, and 
      caused production and release of cytokines IL-8 and RANTES. IL-4 activation of 
      STAT6 did not cause release of these cytokines. Only fibroblasts produced the 
      eosinophil-recruiting cytokine, eotaxin-1, after treatment with TNF-alpha- plus IL-4. 
      As observed in the cultured cells, allergic stimulation in the in vivo model 
      caused degradation of IkappaB-alpha in conjunctiva, and infiltration of eosinophils and 
      other inflammatory cells. CONCLUSION: Activated NFkappaB was found to be a major 
      transcription factor for the release of cytokines from conjunctival cells and 
      intensification of the allergic response. Inhibition of the NFkappaB pathway by 
      therapeutic drugs may be an important objective for the treatment of human 
      allergic conjunctivitis.
FAU - Sakai, Osamu
AU  - Sakai O
AD  - Senju Laboratory of Ocular Sciences, Senju Pharmaceutical Co. Ltd., Kobe, Japan.
FAU - Tamada, Yoshiyuki
AU  - Tamada Y
FAU - Shearer, Thomas R
AU  - Shearer TR
FAU - Azuma, Mitsuyoshi
AU  - Azuma M
LA  - eng
PT  - Journal Article
DEP - 20130426
PL  - England
TA  - Curr Eye Res
JT  - Current eye research
JID - 8104312
RN  - 0 (Chemokine CCL11)
RN  - 0 (Chemokines)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL11/immunology/metabolism
MH  - Chemokines/immunology/*metabolism
MH  - Conjunctiva/cytology/immunology/*metabolism
MH  - Conjunctivitis, Allergic/immunology/*metabolism
MH  - Culture Media, Conditioned/pharmacology
MH  - Epithelial Cells/cytology/immunology/metabolism
MH  - Fibroblasts/cytology/immunology/metabolism
MH  - Interleukin-4/immunology/metabolism
MH  - Interleukin-8/immunology/metabolism
MH  - Male
MH  - Mast Cells/cytology/immunology/metabolism
MH  - NF-kappa B/immunology/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - STAT6 Transcription Factor/metabolism
MH  - Tumor Necrosis Factor-alpha/immunology/metabolism
EDAT- 2013/04/30 06:00
MHDA- 2014/02/12 06:00
CRDT- 2013/04/30 06:00
PHST- 2013/04/30 06:00 [entrez]
PHST- 2013/04/30 06:00 [pubmed]
PHST- 2014/02/12 06:00 [medline]
AID - 10.3109/02713683.2013.780623 [doi]
PST - ppublish
SO  - Curr Eye Res. 2013 Aug;38(8):825-34. doi: 10.3109/02713683.2013.780623. Epub 2013 
      Apr 26.