TLR4-mediated Activation of Monocytes by Human α_S1-Casein

Human milk protein α_S1-casein (CSN1S1) was shown to be overexpressed in autoimmune diseases (osteoarthritisbenign prostatic hyperplasia, multiple sclerosis) as well as in cancer. CSN1S1 displays opioid-like activity and modulates the innate immune response of intestinal cells. Recently, it was demonstrated, that CSN1S1 induces the expression of proinflammatory cytokines (IL‑1β and IL‑6) in monocytic cells via MAPK-p38 signaling [1, 2].

In this study the human TLR4 receptor, a receptor of the innate immune system, was identified as interaction partner of human CSN1S1 inducing expression of cytokines IL‑1β, IL‑6 and IL‑8 in human monocytic cells concentration- and time-dependently [3]. In transfected HEK293 cells expressing TLR4, human CSN1S1 (purified from Escherichia coli) induced secretion of chemokine IL-8. In vitro flow cytometric assays confirmed CSN1S1 - TLR4 receptor interaction. Chemokine secretion as well as binding was not detected for CSN1S1 phosphorylated by protein kinase CK2 as well as for heat denaturated CSN1S1. This supports the hypothesis, that CSN1S1 is a ligand of the TLR4 receptor exerting proinflammatory properties in a phosphorylation-dependent manner.

Literature:

[1] S. Vordenbäumen, et al. BMC Immunol, 2013, 14, 46.

[2] S. Vordenbäumen, et al. J Immunol, 2011, 186, 592.

[3] S. Vordenbäumen, T. Saenger et al. Mol Nutr Food Res, 2016, 60, 1079.