Cysteine proteases: destruction ability versus immunomodulation capacity in immune cells

Abstract

Cysteine proteases (cathepsins) play a pivotal role in various physiological processes, as well as in several diseases. In the immune response, maturation of major histocompatibility class II (MHC II) molecules and processing of antigens for further presentation by MHC II is tightly linked to the enzymes of the endosomal/lysosomal system, of which cysteine proteases constitute a major proportion. Furthermore, the process of autophagy provides access for cytosolic antigens to proteolysis by lysosomal cathepsins and subsequent MHC II presentation. Other specific functions of proteolytic enzymes associated with the immune response, such as activation of granzymes by cathepsin C in T-lymphocytes, are introduced and covered in this review.

Processing of HEBP1 by Cathepsin D Gives Rise to F2L, the Agonist of Formyl Peptide Receptor 3

“…Deregulated CTS D activity (altered expression, increased secretion, or unbalance between protease and endogenous inhibitors) is a factor contributing to various diseases characterized by a chronic inflammatory state, such as cancer, asthma, atherosclerosis, Alzheimer's disease, periodontitis, rheumatoid arthritis, inflammatory bowel disease, osteoarthritis, and pulmonary fibrosis (reviewed in Ref. 41). …”

Cathepsin L in Normal and Pathological Bone Remodeling

“…Although Cathepsin L appears to be primarily a ''housekeeping enzyme,'' several studies indicate that it may harbor important functions outside of lysosomes. Compelling evidence, in this regard, shows that the enzyme also appears to be implicated in the regulation of other important biological processes such as apoptosis and tissue homeostasis [15,[34][35][36][37], immune response [15,[38][39][40], hormone production and processing [41,42] and activation of latent forms of other proteolytic enzymes [6,15,[43][44][45]. Interestingly, growing evidence suggests that Cathepsin L may also have a role in the regulation of bone resorption in normal and pathological conditions [6,15,35,[46][47][48][49][50][51].…”

Cell death during sepsis: integration of disintegration in the inflammatory response to overwhelming infection

“…While caspases are localized predominantly in the cytoplasm, cathepsins reside inside the lysosomes. Cathepsins are involved in a number of important processes, including intracellular protein turnover, antigen processing, proprotein and hormone activation [37,38]. Cathepsins are synthesized as inactive proenzymes and when released into the cytoplasm, they can catalyze enzymatic cleavage of different vital substrates, inducing apoptotic cell death.…”