Immunobiology of S100A8 and S100A9 Proteins and Their Role in Acute Inflammation and Sepsis

Abstract

Toll-like receptors (TLRs) constitute a protein family of cellular receptors that mediate the recognition of microbial challenges and the subsequent inflammatory response. The role of these receptors in allergic diseases of airways remains unclear. The objective of this study was to evaluate TLR2 and TLR4 expression in the lung in a murine model of bronchial hypersensitivity to Aspergillus fumigatus. Different groups of 5-month-old mice (Balb/c) were housed in cages containing hay bedding that was contaminated with A. fumigatus and were kept in an isolation room for 16 days to allow for the induction of allergic airway inflammation. The mice were then exposed once again to Aspergillus spores for 0, 2, 6, 12 and 24 hours; the mice were then sacrificed to obtain bronchoalveolar lavage fluid (BALF) or lung tissues for histology analysis; TLR2 and TLR4 expression. An unexposed group was used as a control. The results indicated that in this allergic mouse model, during the first hours of exposure to A. fumigatus spores in mice previously sensitized to this fungus, there is a decrease in the expression of TLR2 and TLR4 receptors with a concomitant increase in neutrophils in the BALF and histological changes associated with bronchial hyper responsiveness. The difference between our results and those of other studies could be due to the timing, dose, site and intensity of exposure of allergen, environmental factors and host genetic predisposition. This may explain the disparate results of TLR receptor expression during the development of allergies and airway inflammation.

Top-Down Proteomics of Human Saliva Highlights Anti-inflammatory, Antioxidant, and Antimicrobial Defense Responses in Alzheimer Disease

“…During inflammation, S100A8 and S100A9 are actively released and exert a critical role in modulating the inflammatory response by stimulating leukocyte recruitment and inducing cytokine secretion. S100A8 and S100A9 may play a dual role in inflammation, and their pro-inflammatory activity can switch to anti-inflammatory probably depending on the local microenvironment ( El Gazzar, 2015 ). Our results did not allow us to establish if the increased levels of S100A9 and S100A8 observed in saliva of AD patients were linked to a pro- or anti-inflammatory role; however, they agree with studies performed by other research groups.…”

“…Oxidation may represent a switch, whereby the modified proteins display anti-inflammatory functions, such as that demonstrated for S100A8-SNO ( Lim et al, 2008 ); S100A9 and S100A8 are able also to act as ROS/RNS scavengers; in particular, S100A8 is sensitive to oxidative cross-linking and massive oxidation and shows capacity to reduce oxidative damage ( Goyette and Geczy, 2011 ). Changes in the inflammatory microenvironment, PTMs of S100A8 and S100A9, binding with transition metals (Zn 2+ and Ca 2+ ), and S100A8/S100A9 heterodimer formation most likely play an important role in the functional switching of these pleiotropic proteins ( El Gazzar, 2015 ).…”

Myeloid-Derived Suppressor Cells in Sepsis

“…S100A9 translocates into the nucleus to upregulate the transcription of microRNAs miR-21 and miR-181b that fine tune the expansion and the functions of MDSCs. Mice lacking S100A9 have less splenic and bone marrow MDSCs especially during late sepsis and are protected from death (61, 62). In vivo blockade of miR-21 and miR-181 decreases bone marrow MDSCs and improves sepsis survival (63).…”

Effect of zinc supplementation on relative expression of immune response genes in neonates with sepsis: A preliminary study

“…A link was found between S100A8 and S100A9 protein expression and sepsis pathophysiology 9 . The study showed that increase in S100A8/A9 protein complex occurred systemically during Escherichia coli -induced abdominal sepsis in mice 10 .…”

“…Activation of p38 mitogen-activated protein kinases phosphorylates S100A9. Intracellularly, this complex binds to actin resulting in cytoskeletal reorganization and when released extracellularly, it mediates inflammatory mediators 9 .…”