Mp. Vincenti et Ce. Brinckerhoff, Early response genes induced in chondrocytes stimulated with the inflammatory cytokine interleukin-1 beta, ARTHRITIS R, 3(6), 2001, pp. 381-388
Recent work has established that IL-1 beta plays a central role in the infl
ammation and connective tissue destruction observed in both rheumatoid arth
ritis and osteoarthritis. These processes result from the ability of this i
nflammatory cytokine to activate expression of genes for neutral proteases,
such as the matrix metalloproteinases. While IL-1 beta activates matrix me
talloproteinase genes within several hours, it also activates immediate ear
ly genes, which are required for the later expression of matrix metalloprot
einases and other arthritis-perpetuating genes, are also activated. To iden
tify putative immediate early genes involved in IL-1 beta -mediated arthrit
ic disease, a chondrocytic cell line (SW1353) was stimulated with this cyto
kine for 2 hours, total RNA was isolated, and expressed genes were identifi
ed by microarray analysis. This analysis identified alterations in the expr
ession of multiple transcription factors, cytokines, growth factors and the
ir receptors, adhesion molecules, proteases, and signaling intermediates th
at may contribute to inflammation and cartilage destruction in arthritis. I
nterestingly, confirmation of the expression of activating protein-1 family
members by reverse transcriptase polymerase chain reaction revealed a pref
erential increase in junB, a known transcriptional antagonist of c-jun. The
failure to observe induction of early growth response gene-1, which was de
tected by reverse transcriptase polymerase chain reaction to be substantial
ly and transiently induced by 1 hour of IL-1 treatment, may be explained by
the known instability of the message after early induction. However, this
analysis has identified numerous IL-1 beta -responsive genes that warrant f
urther investigation as mediators of disease in arthritis.