Mechanisms of interieukin-1 beta release

作者：Eder Claudia^*

来源：Immunobiology, 2009, 214(7): 543-553.

DOI：10.1016/j.imbio.2008.11.007

• Cytokine
• Inflammasome
• Interleukin-1
• Leukocytes
• Non-classical release

Interleukin-1 beta (IL-1 beta) is a potent proinflammatory cytokine that initiates and amplifies a wide variety of effects associated with innate immunity and host responses to microbial invasion and tissue injury. Production and release of IL-1 beta are stimulated by either pathogen-associated molecular pattern molecules (PAMPs) or damage-associated molecular pattern molecules (DAMPs) and involve several steps. IL-1 beta is first synthesized as biologically inactive pro-IL-1 beta, then processed into mature, biologically active IL-1 beta by caspase-1, and subsequently released into the extracellular milieu. Whereas a large body of recent publications has greatly increased our knowledge of the mechanisms involved in production and processing of IL-1 beta, we are only beginning to understand mechanisms of IL-1 beta P secretion. This review highlights the different models of a non-classical secretory pathway used by monocytes, macrophages and dendritic cells to export the leaderless cytokine IL-1 beta. In particular, five different release mechanisms have been suggested, namely (i) exocytosis of IL-1 beta-containing secretory lysosomes, (ii) release of IL-1 beta from shed plasma membrane microvesicles, (iii) fusion of multivesicular bodies with the plasma membrane and subsequent release of IL-1 beta-containing exosomes, (iv) export of IL-1 beta through the plasma membrane using specific membrane transporters, and (v) release of IL-1 beta upon cell lysis. Reasons for the diversity of IL-1 beta secretory pathways remain to be elucidated. A better understanding of IL-1 beta release mechanisms is of great therapeutic relevance and may help in the development of strategies aimed at reducing the severity of inflammatory and autoimmune diseases.

• 出版日期2009-7