S100A12 is a small protein found within the human body. It is also known as calgranulin C or EN-RAGE (Extracellular Newly Identified RAGE-binding protein). This molecule is involved in various biological processes, contributing to how the body responds to internal and external signals.
What S100A12 Does
S100A12 belongs to the S100 family of proteins, characterized by their ability to bind calcium. This calcium-binding allows it to undergo structural changes, enabling interactions with other molecules. S100 proteins, including S100A12, are found in the cytoplasm or nucleus of various cells, influencing processes like cell cycle progression and differentiation.
This protein is predominantly found in immune cells, such as neutrophils, monocytes, and activated macrophages. It is also expressed by eosinophils and macrophages in asthmatic airways. S100A12 plays a role in immune responses and cellular communication, influencing the movement and activity of immune cells.
S100A12 and Inflammation
S100A12 contributes to the inflammatory process, particularly during infection or tissue damage. It is released from activated immune cells, such as neutrophils, through a microtubule-mediated pathway. This release allows S100A12 to act as a “danger-associated molecular pattern” (DAMP) molecule, signaling a threat to the immune system.
As a DAMP, S100A12 interacts with specific receptors on immune cells, notably the Receptor for Advanced Glycation End-products (RAGE). This binding activates pro-inflammatory signaling pathways, including the MAP-kinase and NF-kappa-B pathways. Activation of these pathways leads to the production of pro-inflammatory cytokines and chemokines, which recruit more immune cells to the site of inflammation. This, along with the up-regulation of cell adhesion molecules, intensifies the inflammatory response.
S100A12 also functions as a chemoattractant, drawing monocytes and mast cells to inflammatory sites. It can stimulate the degranulation and activation of mast cells, which releases chemokines, histamine, and cytokines, inducing leukocyte recruitment to inflamed areas. S100A12 amplifies and sustains inflammatory responses in the body.
S100A12 in Disease
The inflammatory role of S100A12 connects it to various human diseases where its levels are elevated or it contributes to disease progression. S100A12 serves as a biomarker for several inflammatory conditions, making its measurement valuable in clinical settings. High concentrations of S100A12 are found in the serum of patients with inflammatory disorders such as rheumatoid arthritis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis.
In inflammatory bowel diseases, S100A12 levels correlate with disease activity and can help predict disease relapse. Measuring S100A12 can assist in diagnosing these conditions, monitoring their activity, or predicting a patient’s response to treatment. It has also been associated with Kawasaki disease and may play a role in monitoring kidney damage in glomerulonephritis in patients with lupus.
Research explores S100A12 as a potential therapeutic target. Its ability to influence immune cell recruitment and inflammatory signaling pathways suggests that modulating its activity could offer new approaches for managing chronic inflammatory diseases. Understanding its specific interactions and mechanisms in different disease contexts is a focus of scientific investigation.