IAPs and RIPK1 mediate LPS-induced cytokine production in healthy subjects and Crohn's disease
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IAPs and RIPK1 mediate LPS-induced cytokine production in healthy subjects and Crohn's disease. / Seidelin, Jakob Benedict; Jensen, Simone; Hansen, Morten; Bronze, Mariana Rodrigues de Carvalho; Cuchet-Lourenҫo, Delphine; Nejentsev, Sergey; LaCasse, Eric Charles; Nielsen, Ole Haagen.
In: Clinical and Experimental Immunology, Vol. 215, No. 3, 2024, p. 291–301.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - IAPs and RIPK1 mediate LPS-induced cytokine production in healthy subjects and Crohn's disease
AU - Seidelin, Jakob Benedict
AU - Jensen, Simone
AU - Hansen, Morten
AU - Bronze, Mariana Rodrigues de Carvalho
AU - Cuchet-Lourenҫo, Delphine
AU - Nejentsev, Sergey
AU - LaCasse, Eric Charles
AU - Nielsen, Ole Haagen
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2024
Y1 - 2024
N2 - Innate immune activity fuels intestinal inflammation in Crohn's disease (CD), an inflammatory bowel disease (IBD). Identification and targeting of new molecular regulators of the innate activity are warranted to control the disease. Inhibitor of apoptosis proteins (IAPs) regulate both cell survival and inflammatory signaling. We investigated effects of IAP inhibition by second mitochondria-derived activator of caspases (SMAC) mimetics (SMs) on innate responses and cell death to pathogen-associated molecular patterns in peripheral blood mononuclear cells (PBMCs) and monocytes. IAPs inhibited lipopolysaccharide (LPS)-induced expression of proinflammatory interleukin (IL)-1β, IL-6. Likewise, LPS (but not muramyl dipeptide or E. coli) induced TNF-α was inhibited in CD and control PBMCs. The SM effect was partially reversed by inhibition of receptor-interacting serine/threonine-protein kinase 1 (RIPK1). The effect was mainly cell death independent. Thus, IAP inhibition by SMs leads to reduced production of proinflammatory cytokines and may be considered in the efforts to develop new therapeutic strategies to control CD.
AB - Innate immune activity fuels intestinal inflammation in Crohn's disease (CD), an inflammatory bowel disease (IBD). Identification and targeting of new molecular regulators of the innate activity are warranted to control the disease. Inhibitor of apoptosis proteins (IAPs) regulate both cell survival and inflammatory signaling. We investigated effects of IAP inhibition by second mitochondria-derived activator of caspases (SMAC) mimetics (SMs) on innate responses and cell death to pathogen-associated molecular patterns in peripheral blood mononuclear cells (PBMCs) and monocytes. IAPs inhibited lipopolysaccharide (LPS)-induced expression of proinflammatory interleukin (IL)-1β, IL-6. Likewise, LPS (but not muramyl dipeptide or E. coli) induced TNF-α was inhibited in CD and control PBMCs. The SM effect was partially reversed by inhibition of receptor-interacting serine/threonine-protein kinase 1 (RIPK1). The effect was mainly cell death independent. Thus, IAP inhibition by SMs leads to reduced production of proinflammatory cytokines and may be considered in the efforts to develop new therapeutic strategies to control CD.
U2 - 10.1093/cei/uxad092
DO - 10.1093/cei/uxad092
M3 - Journal article
C2 - 37583360
VL - 215
SP - 291
EP - 301
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
SN - 0009-9104
IS - 3
ER -
ID: 364502173