Naslov
CL097, A TLR7/8 ligand, inhibits TLR-4-depemdent activation of IRAK-M and Bcl-3 expression

Autori
Petričević, Branka ; Wessner, Barbara ; Sachet, Monika ; Vrbanec, Damir ; Spittler, Andreas ; Bergmann, Michael

Izvornik
Shock (1073-2322) 32 (2009), 5; 484-490

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
immunosuppresion; LPS; TLR; IRAK-M; Bcl-3; cytokines

Sažetak
Prolonged or repeated stimulation of Toll-like receptor (TLR) 4 leads to hyporesponsiveness of monocyte-derived macrophages, which seems to be a hallmark of immunosuppression related to sepsis and cancer. Two negative regulators of TLR-4 signaling are IL-1 receptor-associated kinase M and B-cell leukemia 3. Here, we demonstrate that the expression of both proteins is inhibited when the TLR-7/TLR-8 agonist CL097 is added to monocyte cultures despite costimulation with the TLR-4 agonist LPS or hyaluronic acid. Reduction of IL-1 receptor-associated kinase M and B-cell leukemia 3 was paralleled by a significant increased cytokine induction of TNF-α, IL-10, and IL-12 observed after intracellular and extracellular TLR stimulation. In ex vivo stimulated whole blood of patients who have prolonged sepsis or metastatic cancer, TLR-7/TLR-8 agonists retained their ability of increased stimulation of TNF-α. These data might add to the understanding of sepsis and cancer-associated immune suppression in men.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA