Abstract
Inflammation is a natural defence mechanism of the body to protect against pathogens. It is induced by immune cells, such as macrophages and neutrophils, which are rapidly recruited to the site of infection, mediating host defence. The processes for eliminating inflammatory cells after pathogen clearance are critical in preventing sustained inflammation, which can instigate diverse pathologies. During chronic inflammation, the excessive and uncontrollable activity of the immune system can cause extensive tissue damage. New therapies aimed at preventing this over-activity of the immune system could have major clinical benefits. Here, we investigated the role of the pro-survival Bcl-2 family member A1 in the survival of inflammatory cells under normal and inflammatory conditions using murine models of lung and peritoneal inflammation. Despite the robust upregulation of A1 protein levels in wild-type cells upon induction of inflammation, the survival of inflammatory cells was not impacted in A1-deficient mice compared to wild-type controls. These findings indicate that A1 does not play a major role in immune cell homoeostasis during inflammation and therefore does not constitute an attractive therapeutic target for such morbidities.
Highlights
Inflammation is an important innate immune response which is usually activated by the ligation of pattern recognition receptors (PRRs) leading to upregulation of a broad range of pro-inflammatory factors, including cytokines and chemokines and migration of leukocytes from the circulation to the site of tissue damage 1
A1 protein expression was analysed by Western blotting of lung tissues and peritoneal lavage cells from wild-type (WT) and A1 knockout (A1−/−) mice that had been challenged with indicated inflammatory stimuli using a previously characterised antibody[17]
Neutrophil apoptosis during resolution of inflammation is necessary for their subsequent engulfment by macrophages 26
Summary
Inflammation is an important innate immune response which is usually activated by the ligation of pattern recognition receptors (PRRs) leading to upregulation of a broad range of pro-inflammatory factors, including cytokines and chemokines and migration of leukocytes from the circulation to the site of tissue damage 1. The clearance of these cells once the infection or injury have been resolved is crucial for the tissue healing process. A1 (in humans called BFL-1), remains a relatively poorly characterised anti-apoptotic protein 3. The identification of BCL2A1 as an NF-kB target gene 6 and its expression in inflammatory cells suggest a role for A1 during inflammation
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