Regulation of immune response by S‑1‑propenylcysteine through autophagy‑mediated protein degradation (Review)

Abstract

Autophagy is a key event in cellular recycling processes due to its involvement in the intracellular degradation of proteins. It has been demonstrated that S−1-propenylcysteine (S1PC), a characteristic sulfur compound in aged garlic extract, induces the activation of autophagy. S1PC degrades the adaptor protein myeloid differentiation response protein 88 (MyD88) of downstream of Toll-like receptor (TLR) by activating autophagy in vitro and in vivo. The degradation of MyD88 inhibits the TLR signaling pathway, including the phosphorylation of interleukin 1 receptor associated kinase 4 (IRAK4) and nuclear factor (NF)-κB p65 in vitro, and eventually leads to the inhibition of interleukin (IL)-6 production in vitro and C-C motif chemokine ligand 2 (Ccl2) mRNA expression in vivo. S1PC also increases the level of intestinal immunoglobulin A (IgA) and the number of IgA-producing cells in Peyer's patches in vivo. In addition, S1PC triggers the mRNA expression of X-box binding protein 1 (Xbp1), an inducer of IgA-producing cell differentiation via the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and the degradation of paired box protein 5 (Pax5), a suppressor of Xbp1 mRNA expression. The present review summarizes the mechanisms through which the activation of autophagy by S1PC modulates the immune response.