Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26324771
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Lee SY
; Jung YO
; Kim DJ
; Kang CM
; Moon YM
; Heo YJ
; Oh HJ
; Park SJ
; Yang SH
; Kwok SK
; Ju JH
; Park SH
; Sung YC
; Kim HY
; Cho ML
J Immunol
2015[Oct]; 195
(7
): 3001-10
PMID26324771
show ga
IL-23 is the key cytokine that induces the expansion of Th17 cells. It is
composed of p19 and p40 subunits of IL-12. The p40 subunit binds competitively to
the receptor of IL-23 and blocks its activity. Our aim was to assess the
preventive and therapeutic effect of the IL-12p40 homodimer (p40)2 subunit in
autoimmune arthritis animal models. In the current study, using IL-1R
antagonist-knockout mice and a collagen-induced arthritis model, we investigated
the suppressive effect of (p40)2 on inflammatory arthritis. We demonstrated that
the recombinant adenovirus-expressing mouse (p40)2 model prevented the
development of arthritis when given before the onset of arthritis. It also
decreased the arthritis index and joint erosions in the mouse model if
transferred after arthritis was established. (p40)2 inhibited the production of
inflammatory cytokines and Ag-specific T cell proliferation. It also induced
CD4(+)CD25(+)Foxp3 regulatory T (Treg) cells in vitro and in vivo, whereas the
generation of retinoic acid receptor-related organ receptor ?t and Th17 cells was
suppressed. The induction of Treg cells and the suppression of Th17 cells were
mediated via activated STAT5 and suppressed STAT3. Our data suggest that (p40)2
suppressed inflammatory arthritis successfully. This could be a useful
therapeutic approach in autoimmune arthritis to regulate the Th17/Treg balance
and IL-23 signaling.
|Animals
[MESH]
|Arthritis, Experimental/drug therapy/immunology/*prevention & control
[MESH]
free
free
free
