Increased expression of interleukin-12 receptor beta(2) on lamina propria mononuclear cells of patients with active Crohn's disease.
OBJECTIVE
Since interleukin-12 is pathogenetically involved in Crohn's disease (CD) but not in ulcerative colitis (UC), expression and mechanisms of induction of interleukin-12 receptor (IL-12R) subunits beta(1) and beta(2) were analyzed in lamina propria mononuclear cells (LPMNC) of patients with CD and UC.


METHODS
LPMNC from patients with CD ( n=17), UC ( n=14), and controls ( n=19) were isolated by standard techniques. IL-12R beta(1) and IL-12R beta(2) transcripts were semiquantified by RT-PCR, and expression of IL-12R beta(2) chain was characterized by flow cytometry. LPMNC were activated by cross-linking with anti-CD3 antibodies and B7-1 costimulation.


RESULTS
IL-12R beta(1) and IL-12R beta(2) transcript concentrations were higher in inflamed specimens than in noninflamed segments of patients with CD but not in UC. Increased percentage of mucosal CD4(+)/IL-12R beta(2)(+) cells was observed in active CD, but not UC. In vitro stimulation of LPMNC with anti-CD3 antibodies resulted in an increase in IL-12R beta(1) transcripts irrespective of B7-1 mediated costimulation (84% and 95%, respectively). However, increased expression of IL-12R beta(2) mRNA (110%) was detected only after B7-1 costimulation.


CONCLUSIONS
Our data indicate that increased mucosal expression of IL-12R beta(2) on LPMNC in CD but not in UC may be the result of B7-1 costimulation. Modulation or inhibition of IL-12R beta(2) expression on LPMNC could provide a selective therapeutic approach in CD.
Stallmach
A
A
Department of Internal Medicine II, Saarland University, 66421 Homburg, Germany. inasta@uniklinik-saarland.de
Marth
T
T
Adrian
N
N
Wittig
B M
BM
Ecker
K-W
KW
Schilling
M
M
Zeitz
M
M
D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000150:complications / Q000378:metabolism; D003424:Crohn Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D005858:Germany; D006801:Humans; D053646:Interleukin-2 Receptor beta Subunit; D007413:Intestinal Mucosa / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012322:RNA Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis*
C508020:IL2RB protein, human; D053646:Interleukin-2 Receptor beta Subunit; D012322:RNA Precursors; D012333:RNA, Messenger; D018123:Receptors, Interleukin