Autophagy and inflammation

Abstract

Autophagy is a homeostatic mechanism involved in the disposal of damaged organelles, denatured proteins as well as invaded pathogens through a lysosomal degradation pathway. Recently, increasing evidences have demonstrated its role in both innate and adaptive immunity, and thereby influence the pathogenesis of inflammatory diseases. The detection of autophagy machinery facilitated the measurement of autophagy during physiological and pathophysiological processes. Autophagy plays critical roles in inflammation through influencing the development, homeostasis and survival of inflammatory cells, including macrophages, neutrophils and lymphocytes; effecting the transcription, processing and secretion of a number of cytokines, as well as being regulated by cytokines. Recently, autophagy-dependent mechanisms have been studied in the pathogenesis of several inflammatory diseases, including infectious diseases, Crohn's disease, cystic fibrosis, pulmonary hypertension, chronic obstructive pulmonary diseases and so on. These studies suggested that modulation of autophagy might lead to therapeutic interventions for diseases associated with inflammation. Here we highlight recent advances in investigating the roles of autophagy in inflammation as well as inflammatory diseases.

Keywords: Autophagy; Inflammation; Inflammatory diseases.

Fig. 1

Induction and mechanisms of autophagy in mammalian cells. The process of autophagy involves two major steps: induction of autophagosome and fusion of autophagosome with lysosome. The ULK/Atg1 kinase complex, the autophagy-specific PI3-kinase complex, and PI(3)P effectors and their related proteins are important for the nucleation step, whereas the Atg12- and LC3/Atg8-conjugation systems are important for the elongation step. In addition, other proteins required for autophagosome-lysosomal fusion, lysosomal acidification, and lysosomal digestion, and regulatory signals that integrate environmental cues with the autophagic machinery are involved in autophagy

Fig. 2

Effects of autophagy in inflammatory cells. Autophagy influences the development, homeostasis and survival of inflammatory cells, including macrophages, neutrophils and T lymphocytes and B lymphocytes

Fig. 3

The interactions of autophagy and inflammatory cytokines or chemokines. Autophagy can affect the secretion of cytokines by itself, including Th1 cytokines, IFN-γ, TNF-α, IL-1, IL-2, IL-6, TGF-β, MCP-1 and Th2 cytokines, IL-4, IL-10 and IL-13, as well as other cytokines, IL-1β, IL-18, IFN-a, IFN-β, IL-8