The effects of Kv1.3 and IKCa1 channel inhibition on cytokine production and calcium influx of T lymphocytes in rheumatoid arthritis and ankylosing spondylitis.
Kv1.3 and IKCa1 lymphocyte potassium channels have been implicated as important targets of selective immunomodulation. We compared the alterations in cytokine production upon selective inhibition of Kv1.3 or IKCa1 channels (by MGTX and TRAM, respectively) in healthy donors (HD), RA and AS patients. We also determined calcium influx kinetics and its sensitivity to Kv1.3 and IKCa1 channel inhibition following PHA activation in CD4, Th1, Th2 and CD8 cells as well as monocytes. The application of TRAM resulted in a lower production of TNF-a and IL1-RA in all three study groups. Inhibition by TRAM had contrary effects on the production of IL-1b and IL-5: While their production was increased by PBMCs of RA patients, this effect was not observed in HD and AS PBMCs. While treatment with MGTX resulted in a similar decrease in calcium influx in the CD4 and Th2 subsets across all study groups, TRAM treatment had opposite effects on RA and HD samples: It decreased calcium influx in the Th2 and CD8 subsets in RA, while only Th1 cells were affected in HDs. The effects of IKCa1 channel inhibition are controversial in samples of RA and AS patients, since it shifts the inflammatory balance into the pro-inflammatory direction.
First Department of Pediatrics, Semmelweis University, Bókay u. 53, Budapest, 1083, Hungary. toldigergely@yahoo.com.|MTA-SE, Pediatrics and Nephrology Research Group, Budapest, Hungary. toldigergely@yahoo.com.
Gergely
G
Toldi
Department of Internal Medicine 3, University of Erlangen-Nürnberg, Erlangen, Germany.
Luis
L
Munoz
Department of Internal Medicine 3, University of Erlangen-Nürnberg, Erlangen, Germany.
Martin
M
Herrmann
Department of Internal Medicine 3, University of Erlangen-Nürnberg, Erlangen, Germany.
Georg
G
Schett
Department of Rheumatology, University of Szeged, Szeged, Hungary.
Attila
A
Balog
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors*; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000276:immunology* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
D016207:Cytokines; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D051664:Kv1.3 Potassium Channel; D002118:Calcium
AS; Calcium influx; Cytokine; IKCa1; Kv1.3; RA