Gasdermin Family Antibody Sampler Kit

Background

The gasdermin family, which includes GSDMA, GSDMB, GSDMC, GSDMD, and GSDME, has been shown to play a role in inflammation and cell death. Gasdermin D has been reported to have a critical role as a downstream effector of pyroptosis (1,2). Pyroptosis is a lytic type of cell death triggered by inflammasomes, multiprotein complexes assembled in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) that result in the activation of caspase-1 and subsequent cleavage of pro-inflammatory cytokines IL-1β and IL-18 (3). Gasdermin D was identified by two independent groups as a substrate of inflammatory caspases, caspase-1 and caspase-11/4/5, producing two fragments: GSDMD-N and GSDMD-C. Cleavage results in release of an intramolecular inhibitory interaction between the N- and C-terminal domains, allowing the N-terminal fragment GSDMD-N to initiate pyroptosis through the formation of pores on the plasma membrane (4-7).

Like other gasdermin family members, Gasdermin E (also called DFNA5) contains an amino-terminal pore forming domain that triggers pyroptosis. Cleavage of Gasdermin E at Asp270 is induced by apoptotic-associated caspase-3, converting apoptotic signals to pyroptosis (8). In addition, cleavage of Gasdermin E can be induced by Granzyme B secreted by NK cells and contributes to tumor suppressive activity (9). Gasdermin E expression is suppressed in several types of cancer, including gastric, colorectal, and breast carcinoma, and may be associated with decreased survival (10-12). In contrast, an increase in Gasdermin E, including the amino-terminal pore-forming fragment, is associated with conditions of excessive inflammation (13-15). Gasdermin A (GSDMA) is preferentially expressed in the epithelium of the skin and gastrointestinal tract and is frequently suppressed in gastric cancer (16-18). Gasdermin B (GSDMB) has been reported to be upregulated in several tumor types, and in breast cancer has been associated with metastasis and poor prognosis (19,20). In addition, Gasdermin B has been associated with immune disorders, including asthma (21,22). Gasdermin B can be cleaved by Granzyme A secreted from cytotoxic lymphocytes leading to pyroptotic cell death (23).