Laboratory of Toxicology, Department of Environmental Science and Policy, Università degli Studi di Milano, Milan, Italy.
Department of Drug Sciences, Università di Pavia, Pavia, Italy.
Adv Exp Med Biol. 2021;1275:151-163. doi: 10.1007/978-3-030-49844-3_6.
Protein kinase C (PKCs) isoforms play a key regulatory role in a variety of cellular functions, including cell growth and differentiation, gene expression, hormone secretion, etc. Patterns of expression for each PKC isoform differ among tissues, and it is also clear that different PKCs are often not functionally redundant, for example specific PKCs mediate specific cellular signals required for activation, proliferation, differentiation and survival of immune cells. In the last 20 years, we have been studying the role of PKCs, mainly PKCβ and its anchoring protein RACK1 (Receptor for Activated C Kinase 1), in immune cell activation, and their implication in immunosenescence and immunotoxicity. We could demonstrate that PKCβ and RACK1 are central in dendritic cell maturation and activation by chemical allergens, and their expressions can be targeted by EDCs and anti-inflammatory drugs. In this chapter, current knowledge on the role of PKC in immune cell activation and possible implication in immunotoxicity will be described.
蛋白激酶 C(PKC)同工酶在多种细胞功能中发挥关键调节作用,包括细胞生长和分化、基因表达、激素分泌等。每种 PKC 同工酶的表达模式在组织中存在差异,而且不同的 PKC 同工酶通常并非功能冗余,例如,特定的 PKC 同工酶介导免疫细胞激活、增殖、分化和存活所需的特定细胞信号。在过去的 20 年中,我们一直在研究 PKC(主要是 PKCβ及其锚定蛋白 RACK1(激活的 C 激酶受体 1))在免疫细胞激活中的作用,以及它们在免疫衰老和免疫毒性中的意义。我们可以证明 PKCβ和 RACK1 是化学变应原诱导树突状细胞成熟和激活的核心,它们的表达可以被 EDCs 和抗炎药物靶向。本章将描述 PKC 在免疫细胞激活中的作用及其在免疫毒性中的潜在意义的最新知识。