TNF alpha and TGF-beta 1 influence IL-18-induced IFN gamma production through regulation of IL-18 receptor and T-bet expression
Anna Koutoulaki, Martin Langley, Alastair J Sloan, Daniel Aeschlimann, Xiao-Qing Wei
CYTOKINE | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD | Published : 2010
Bacterial infections can lead to a state of uncontrolled inflammation and also trigger autoimmune disease. At the centre of this are CD4(+) T cell responses in inflammatory tissues or local lymph nodes which are orchestrated by dendritic cells. IL-18 is a pro-inflammatory cytokine that drives dendritic cell maturation and mediates IFNgamma production. In this study, we demonstrate that in the dendritic precursor-like cell line KG-1, IFNgamma production induced by IL-18 is potentiated (>5-fold) by TNFalpha and completely suppressed by TGF-beta1. IL-18 stimulation rapidly activates different MAPK signalling pathways but only blocking of p38 activation alleviates IFNgamma production. The mechan..View full abstract
Awarded by Arthritis Research Campaign
This work was supported by a grant from the Arthritis Research Campaign (Grant No. 17212) to X.-Q.W. and D.A. and a Cardiff University studentship to A.K.