Synovial fibroblasts from rheumatoid arthritis patients differ in their regulation of IL-16 gene activity in comparison to osteoarthritis fibroblasts.
BACKGROUND
In rheumatoid arthritis (RA), synovial fibroblast-like cells (SF) contribute significantly to articular inflammation. They express distinct patterns of genes associated with cell proliferation and differentiation and elevated levels of cytokines and chemoattractant factors, including IL-16. Here we investigated pathways regulating IL-16 expression in fibroblasts from RA patients in comparison to fibroblasts from osteoarthritis (OA) patients.


METHODS
Fibroblasts were isolated from dermal and articular biopsies, expanded and pathways of IL-16 induction were investigated by real time quantitative RT/PCR, immuno blot and ELISA.


RESULTS
Stimulation of cAMP dependent signal transduction by forskolin induced prominent IL-16 RT/PCR signals in OA-DF and OA-SF. In contrast, in RA-DF and RA-SF staurosporine significantly augmented IL-16 RT/PCR signals, but forskolin induced less IL-16 transcript amounts. Activation of protein kinase C by PMA induced a significant IL-16 response only in RA-SF. Addition of IL-1beta or TNF-alpha did not upregulate IL-16 mRNA but secretion of the mature IL-16 cytokine was activated in serum starved cells in presence of IL-1beta.


CONCLUSIONS
Our results suggest that RA fibroblasts differ from OA fibroblasts with respect to their sensitivities to kinase/phospatase signal transduction pathways. The enhanced expression of IL-16 in the synovial membrane early in RA vs OA may be associated in part with these distinct signaling responses.
Center for Orthopedic Surgery, UKT University Hospital Tübingen, Germany.
Michaela
M
Weis-Klemm
Dorothea
D
Alexander
Thomas
T
Pap
Heike
H
Schützle
Dorothee
D
Reyer
Juliane K
JK
Franz
Wilhelm K
WK
Aicher
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism*; D002457:Cell Extracts / Q000737:chemistry; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D019410:Interleukin-16 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D019311:Staurosporine / Q000494:pharmacology; D013583:Synovial Membrane / Q000166:cytology*
D002457:Cell Extracts; D007375:Interleukin-1; D019410:Interleukin-16; D012333:RNA, Messenger; D005576:Colforsin; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; D019311:Staurosporine