Human αS1-casein induces IL-8 secretion by binding to the ecto-domain of the TLR4/MD2 receptor complex

Saenger, Thorsten; Vordenbäumen, Stefan; Genich, Swetlana; Haidar, Samer; Schulte, Mona; Nienberg, Christian; Bleck, Ellen; Schneider, Matthias; Jose, Joachim

doi:10.1016/j.bbagen.2018.12.007

Cited by 10 publications

(13 citation statements)

References 50 publications

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“…In general, experiments were performed as described in detail by Saenger et al (2019). Briefly, TLR4-transfected human embryonic kidney (HEK293) cells (TLR4 + cells) and nontransfected control cells (TLR4 − cells) were cultured according to the manufacturer's protocols (InvivoGen, San Diego, USA).…”

Section: Hek293 Cell Culture Il-8 Release and Cell Viabilitymentioning

confidence: 99%

Root Extracts From Ononis spinosa Inhibit IL-8 Release via Interactions With Toll-Like Receptor 4 and Lipopolysaccharide

et al. 2020

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Extracts from the roots of Ononis spinosa L. (restharrow roots) are traditionally used for the treatment of patients with urinary tract infections due to its mild diuretic activity, caused by the inhibition of renal human hyaluronidase-1 by isoflavonoids. Preliminary studies also indicated anti-inflammatory effects. The following study aimed at investigating potential anti-inflammatory effects of restharrow extracts, prepared with solvents of different polarity. A dichloromethane extract (OS1), mainly composed of isoflavonoids and triterpenes as characterized by LC-MS, showed a concentration-dependent (25-100 mg/ml) inhibition of IL-8 and TNF-a release from LPS-stimulated human neutrophils. Significant inhibition was also found for the triterpene a-onocerin and the norneolignan clitorienolactone B, isolated from OS1. Further, OS1 and both compounds significantly decreased the expression of the adhesion molecules CD11b/CD18 and conversely increased the expression of CD62L in LPS-stimulated human neutrophils. This finding corresponds to a reduced inflammatory response by the inhibition of adhesion and migration of immune cells. As all of the observed effects are potentially mediated via Tolllike receptor 4 (TLR4) signaling, TLR4 transfected HEK293 cells were incubated with OS1. LPS-induced IL-8 secretion was significantly inhibited in a concentration-dependent manner, confirming TLR4 antagonism. This inhibition, however, was in part caused by an interaction of OS1 with LPS. In addition, also an aqueous extract containing high amounts of isoflavonoid glycosides and saponins from the roots of O. spinosa showed anti-inflammatory effects by interacting with the TLR4 signaling pathway. This study rationalizes the traditional use of extracts from O. spinosa for therapy of urinary tract infections, due to its potential anti-inflammatory effects that are mediated via TLR4 receptor antagonism.

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Section: Hek293 Cell Culture Il-8 Release and Cell Viabilitymentioning

confidence: 99%

Root Extracts From Ononis spinosa Inhibit IL-8 Release via Interactions With Toll-Like Receptor 4 and Lipopolysaccharide

et al. 2020

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“…Human unphosphorylated αS1-casein induces Toll-like receptor 4 (TLRs) mediated expression of the proinflammatory cytokines IL-1β, GM-CSF, and IL-6 in monocytic cells [63] and induces the differentiation of monocytes toward macrophages [49,64], but this process is not dependent upon LPS. Interestingly, a posttranslational modification in αS1-casein (a phosphorylation event) inhibits binding to TLR4, which acts as an off switch for proinflammatory effects [48].…”

Section: Inflammation and Immune System Enhancement By Caseinsmentioning

confidence: 99%

“…Ectopic expression (outside the mammary gland) of αS1-casein has been detected in inflamed tissues such as synovial cells and cartilage of rheumatoid arthritis, osteoarthritis, and multiple sclerosis patients [63,[65][66][67], prostate hyperplasia [68], and lymph nodes of encephalomyelitic mice [67]. Hence, αS1-casein may constitute an autogenous stimulus that upholds chronic autoimmune inflammation via TLR4 [64].…”

Section: Inflammation and Immune System Enhancement By Caseinsmentioning

confidence: 99%

“…In this sense, there is evidence that at least β-casein can influence B lymphocytes via TLR4 [76,77], and a recent study showed that casein binds directly to TLR4 of CD8+ T lymphocytes [64], although it has also been shown that β-casein can influence the activation and production of histamine through a kinase-dependent mechanism PI3 [78].…”

Section: Action Mechanism Of Caseins To Induce Hematopoiesis and Immumentioning

confidence: 99%

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Caseins as Regulators of Hematopoiesis

Ledesma‐Martínez¹,

Domínguez-Meléndez²,

Aguíñiga-Sánchez³

et al. 2020

Infant Feeding - Breast Versus Formula

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The main physiological role of casein, the main protein component in the milk, is to be a source of amino acids that are required for the growth of the neonate; therefore, casein is considered a highly nutritious protein. Over time, it has been revealed that casein is a protein whose physiological importance reaches levels far superior to the food field, having a wide array of biological activities including antimicrobial activities, facilitating absorption of nutrients, as well as acting as a growth factor and an immune stimulant. Here we analyze how caseins can exert numerous hematopoietic and immunomodulatory actions, their role in granulopoiesis, monocytopoiesis, and lymphopoiesis from the early stages of postnatal development seemingly throughout life, and we wonder if casein could be useful to fight pathogens resistant to antibiotics, inducing a strong immune response in immunosuppressed patients, or even be a prophylactic strategy to prevent infections.

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“…Consequently, the recognition of TLR4 on antigen-presenting cells enhances antigen-specific antitumour immunity [119, 120], and an immunotherapeutic regimen capable of eliminating large, established mouse tumours has been developed using HMGN1, a DC-activating TLR4 agonist that is capable of inducing antitumour immunity [121]. It has recently been shown that α -casein binds to TLRs [47, 122]; thus, casein could exert immunomodulatory effects on leukocytes and even participate in the genesis of blood cells via TLRs (Figure 1), which could explain the antineoplastic effect of α -casein in WEHI-3 leukaemia cells [116].…”

Section: Mechanism Of Action For Caseins and Derivate Peptides In mentioning

confidence: 99%

Casein and Peptides Derived from Casein as Antileukaemic Agents

Ledesma‐Martínez

Aguíñiga-Sánchez

Weiss‐Steider

et al. 2019

Journal of Oncology

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Milk is a heterogeneous lacteal secretion mixture of numerous components that exhibit a wide variety of chemical and functional activities. Casein, the main protein in milk, is composed of α-, β-, and κ-caseins, each of which is important for nutritional value and for promoting the release of cytokines, also are linked to the regulation of haematopoiesis and immune response and inhibit the proliferation and induce the differentiation of leukaemia cells. It has been shown that the digestive process of caseins leads to the release of bioactive peptides that are involved in the regulation of blood pressure and the inhibition or activation of the immune response by serving as agonists or antagonists of opioid receptors, thus controlling the expression of genes that exert epigenetic control. Later, they bind to opioid receptor, block nuclear factor κ-beta, increase the redox potential, and reduce oxidative stress and the pro-inflammatory agents that favour an antioxidant and anti-inflammatory environment. Therefore, the bioactive peptides of casein could be compounds with antileukaemia potential. This review provides a summary of current knowledge about caseins and casein peptides on the immune system as well as their roles in the natural defence against the development of leukaemia and as relevant epigenetic regulators that can help eradicate leukaemia.

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Human αS1-casein induces IL-8 secretion by binding to the ecto-domain of the TLR4/MD2 receptor complex

Cited by 10 publications

References 50 publications

Root Extracts From Ononis spinosa Inhibit IL-8 Release via Interactions With Toll-Like Receptor 4 and Lipopolysaccharide

Root Extracts From Ononis spinosa Inhibit IL-8 Release via Interactions With Toll-Like Receptor 4 and Lipopolysaccharide

Caseins as Regulators of Hematopoiesis

Casein and Peptides Derived from Casein as Antileukaemic Agents

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