Pyroptosis: a double-edged sword in lung cancer and other respiratory diseases

Abstract

Pyroptosis is an active cell death process mediated by gasdermin family proteins including Gasdermin A (GSDMA), Gasdermin B (GSDMB), Gasdermin C (GSDMC), Gasdermin D (GSDMD), Gasdermin E (GSDME, DFNA5), and DFNB59. Emerging evidences have shown that pyroptosis contributes to many pulmonary diseases, especially lung cancer, and pneumonia. The exact roles of pyroptosis and gasdermin family proteins are tremendously intricate. Besides, there are evidences that pyroptosis contributes to these respiratory diseases. However, it often plays a dual role in these diseases which is a cause for concern and makes it difficult for clinical translation. This review will focus on the multifaceted roles of pyroptosis in respiratory diseases.

Keywords: Caspase; Gasdermin; Lung cancer; Pneumonia; Pyroptosis.

Fig. 1

Activation mechanism of pyroptosis in the respiratory system in the canonical pathway and the non-canonical pathway. In canonical pathway, the NLRP3 inflammasome is taken as a representative example. The NLRP3 inflammasome consists of NLRP3, an important member of NLRs (NOD-like receptors), ASC, and pro-caspase-1. In addition to NLRs and pyrin, absent in melanoma 2 (AIM2) can also form inflammasomes to activate pyroptosis

Fig. 2

Pyroptotic pathway. GSDM superfamily members have six members: Gasdermin A (GSDMA), Gasdermin B (GSDMB), Gasdermin C (GSDMC), Gasdermin D (GSDMD), Gasdermin E (GSDME, DFNA5), and DFNB59. Gasdermins except for DFNB59 have similar architecture of two domains: an N-terminal and a C-terminal. N-terminal domains have pore-forming activities and activate pyroptosis. Pyroptosis has been reported to be involved in many pulmonary diseases. (Solid line: promoting effect, dotted line: inhibiting effect)

Fig. 3

Role of pyroptosis in the lung. This schematic representation shows the important role of pyroptosis in the regulation of pulmonary diseases including pneumonia, asthma, lung cancer COPD, and ALI/ARDS