Anti-Inflammatory Effects of IKK Inhibitor XII, Thymulin, and Fat-Soluble Antioxidants in LPS-Treated Mice

Abstract

The present study was designed to compare the anti-inflammatory effects of several agents applied in vivo, namely, a synthetic inhibitor of the NF-κB cascade, fat-soluble antioxidants, and the thymic peptide thymulin. Cytokine response in LPS-treated mice was analysed in tandem with the following parameters: the synthesis of inducible forms of the heat shock proteins HSP72 and HSP90α; activity of the NF-κB and SAPK/JNK signalling pathways; and TLR4 expression. Inflammation-bearing Balb/c male mice were pretreated with an inhibitor of IKK-α/β kinases (IKK Inhibitor XII); with thymulin; with dietary coenzyme Q9, α-tocopherol, and β-carotene; or with combinations of the inhibitor and peptide or antioxidants. Comparable anti-inflammatory effects were observed in inflammation-bearing mice treated separately with thymulin or with dietary antioxidants administered daily for two weeks before LPS treatment. When LPS-injected mice were treated with the inhibitor and antioxidants together, neither plasma cytokines, signal proteins, nor heat shock proteins recovered more efficiently than when mice were treated with these agents separately. In contrast to antioxidant diet, the thymulin was shown to increase the effect of IKK Inhibitor XII in preventing IKK activation in LPS-treated mice.

Pentacyclic Triterpenoids Inhibit IKKβ Mediated Activation of NF-κB Pathway: In Silico and In Vitro Evidences

“…This is an additional evidence to indicate the ability of the PTs to inhibit the IKK-mediated NF-κB activation and the subsequent suppression of the pro-inflammatory cytokines. Our findings are in accordance with the results from an earlier in vivo study in the LPS-treated mice [ 90 ]. Modulation of the LPS-induced NF-κB signaling by the PTs along with the proposed mechanisms is presented as schematics in Fig 9 .…”

“…The increase in the IKK/NF-κB activity has a critical role in LPS stimulated inflammation. The pretreatment of the LPS treated mice with the IKK inhibitor XII decreases the plasma levels of the IFN-γ, a pro-inflammatory cytokine [ 90 ]. This study substantiates the significance of the IKK inhibition in delaying the proinflammatory response in the LPS-treated mice.…”

Staphylococcus aureus Triggers Induction of miR-15B-5P to Diminish DNA Repair and Deregulate Inflammatory Response in Diabetic Foot Ulcers

“…IKBKB is a positive regulator of the inflammatory response and an important upstream modulator of NF-kB pathway. Its inhibition reduces the inflammatory response and pro-inflammatory cytokine production in response to LPS (Novoselova et al, 2014), and may contribute to diminished ability of DFUs to respond to pathogens. By suppressing the key regulator gene IKBKB, S. aureus -induced miR-15b-5p may affect multiple signaling pathways including NF-KB, IL6, IL8, IL12, PI3K/AKT, and PTEN (Ding et al, 2013, Li et al, 2010) contributing to suppression of the inflammatory phase of wound healing, which is required for a proper healing response and clearing bacterial contamination.…”

Thymulin, free or bound to PBCA nanoparticles, protects mice against chronic septic inflammation

“…In the present work, we aimed to study the effects of thymulin on immune cell activity in a mouse model of chronic inflammation induced by daily treatment with increasing doses of LPS. Based on our earlier investigations, in which thymulin was found to have anti-inflammatory properties in vitro [ 21 ] and in acute inflammation in vivo [ 31 ], we concluded that it might exert a protective effect against the consequences of sepsis. It is important to emphasize that when applied to healthy mice, thymulin does not affect plasma levels of proinflammatory cytokines, synthesis of stress proteins (Hsp70 and Hsp90), or cellular production of nitric oxide [ 31 ].…”

“…Recently, we also extensively studied the role of thymic peptides in the pathogenesis of sepsis [ 19 ]. For the first time, we revealed that the anti-inflammatory effects of such peptides are mediated by the activity of several intracellular signaling pathways [ 20 ], and that one of these peptides, thymulin, increases the anti-inflammatory activity of a specific inhibitor of the NF-κB signaling pathway, IκB kinase (IKK) inhibitor XII, in mice with acute septic inflammation [ 21 ].…”