Anti-Bacterial Agents/therapeutic use* ; Cytokines ; Humans ; Inflammation/drug therapy* ; Pore Forming Cytotoxic Proteins ; Psoriasis/drug therapy*

Perforin and granzyme are important effector molecules in cytolytic cells. They can induce apoptosis of tumor cells and infection cells. The research of biologic missile is noticed with the progress in therapy targeting to the disease. It is supposed that perforin and granzyme play an important role in biological missiles because of their biologic function and structure. A review on several aspects of these effector molecules is presented.
Animals ; Granzymes ; Humans ; Killer Cells, Natural ; immunology ; Membrane Glycoproteins ; immunology ; therapeutic use ; Neoplasms ; immunology ; therapy ; Perforin ; Pore Forming Cytotoxic Proteins ; Serine Endopeptidases ; immunology ; therapeutic use ; T-Lymphocytes, Cytotoxic ; immunology

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.
Humans ; NF-kappa B/metabolism* ; Lipopolysaccharides/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Acute Lung Injury/metabolism* ; Lung ; Phosphate-Binding Proteins/therapeutic use* ; Pore Forming Cytotoxic Proteins/therapeutic use*