Interleukin-20 receptor expression in the trabecular meshwork and its implication in glaucoma.
OBJECTIVE
To determine whether interleukin-20 receptors (IL-20R) are expressed in trabecular meshwork cells and the effect of a T104M mutation in IL-20R2 on downstream cellular functions.


METHODS
Evaluation of signal transducer and activator of transcription (STAT)3 phosphorylation and generic matrix metalloproteinase (MMP) activity in primary open angle glaucoma (POAG) dermal fibroblasts (pHDF) with the T104M IL-20R2 mutation were compared with normal human dermal fibroblasts (HDF). Expression of IL-20R1 and IL-20R2 in human trabecular meshwork (HTM) cells was determined by immunohistochemistry and western immunoblotting.


RESULTS
A T104M mutation in IL20-R2 was identified in a large POAG family in which the GLC1C locus was originally mapped. pHDFs harboring this mutation had significantly increased phosphorylated STAT3 (pSTAT3) activity compared with normal HDFs. However, stimulation with either IL-19 or IL-20 for 15 min resulted in significantly decreased levels of pSTAT3 in pHDFs compared with controls. Generic MMP activity was significantly decreased in pHDFs compared with controls after stimulation with IL-20 for 24 h. Both IL-20R1 and IL-20R2 receptors were expressed in HTM cells by western immunoblot and immunofluorescence, and they appeared to be up-regulated in response to cytokine treatment.


CONCLUSIONS
A T104M mutation in IL-20R2 significantly impacts the function of this receptor as shown by decreased pSTAT3 levels and generic MMP activity. Reduced MMP activity may affect the ability of glaucoma patients to alter outflow resistance in response to elevated intraocular pressure.
Casey Eye Institute, Oregon Health & Sciences University , Portland, Oregon.
Kate E
KE
Keller
Yong-Feng
YF
Yang
Ying Ying
YY
Sun
Renee
R
Sykes
Natalie Donna
ND
Gaudette
John R
JR
Samples
Ted S
TS
Acott
Mary K
MK
Wirtz
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D016022:Case-Control Studies; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005902:Glaucoma, Open-Angle / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D010766:Phosphorylation; D018123:Receptors, Interleukin / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics; D014129:Trabecular Meshwork / Q000378:metabolism*
D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C492510:interleukin-20 receptor; D020782:Matrix Metalloproteinases