BCG vaccine in Korea.

The anti-tuberculosis Bacille de Calmette et Guérin (BCG) vaccine was developed between 1905 and 1921 at Pasteur Institutes of Lille in France, and was adopted by many countries. BCG strains comprise natural mutants of major virulence factors of Mycobacterium tuberculosis and that BCG sub-strains differ markedly in virulence levels. The tuberculosis became endemic in Korea after the Korean War (1950s).

Suppression of Toll-like receptor 4 activation by endogenous oxidized phosphatidylcholine, KOdiA-PC by inhibiting LPS binding to MD2.

Objective: Activation of Toll-like receptor 4 (TLR4) triggers immune and inflammatory events by sensing endogenous danger signals as well as invading pathogens and contributes to the development of chronic inflammatory diseases. In this study, we investigated effect of 1-palmitoyl-2-(5-keto-6-octenedioyl)-sn-glycero-3-phosphocholine (KOdiA-PC), an oxidized phosphatidylcholine, on TLR4 activation and the underlying regulatory mechanism.

Methods: RAW264.

PI3K/Akt contributes to increased expression of Toll-like receptor 4 in macrophages exposed to hypoxic stress.

Toll-like receptors (TLRs) play critical roles in triggering immune and inflammatory responses by detecting invading microbial pathogens and endogenous danger signals. Increased expression of TLR4 is implicated in aggravated inflammatory symptoms in ischemic tissue injury and chronic diseases. Results from our previous study showed that TLR4 expression was upregulated by hypoxic stress mediated by hypoxia-inducible factor-1 (HIF-1) at a transcriptional level in macrophages.

Akt contributes to activation of the TRIF-dependent signaling pathways of TLRs by interacting with TANK-binding kinase 1.

Toll/IL-1R domain-containing adaptor inducing IFN-β (TRIF) is an adaptor molecule that is recruited to TLR3 and -4 upon agonist stimulation and triggers activation of IFN regulatory factor 3 (IRF3) and expression of type 1 IFNs, which are critical for cellular antiviral responses. We show that Akt is a downstream molecule of TRIF/TANK-binding kinase 1 (TBK1) and plays an important role in the activation of IRF3 by TLR3 and -4 agonists. Blockade of Akt by a dominant-negative mutant or by short interfering RNA decreased IRF3 activation and IFN-β expression induced by polyinosinic:polycytidylic acid [poly(I:C)], LPS, TRIF, and TBK1.

Hypoxic stress up-regulates the expression of Toll-like receptor 4 in macrophages via hypoxia-inducible factor.

Toll-like receptors (TLRs) are germline-encoded innate immune receptors that recognize invading micro-organisms and induce immune and inflammatory responses. Deregulation of TLRs is known to be closely linked to various immune disorders and inflammatory diseases. Cells at sites of inflammation are exposed to hypoxic stress, which further aggravates inflammatory processes.

Sulforaphane suppresses oligomerization of TLR4 in a thiol-dependent manner.

TLRs are pattern recognition receptors that detect invading microorganisms and nonmicrobial endogenous molecules to trigger immune and inflammatory responses during host defense and tissue repair. TLR activity is closely linked to the risk of many inflammatory diseases and immune disorders. Therefore, TLR signaling pathways can provide efficient therapeutic targets for chronic diseases.