Serum S100A8 and S100A9 Enhance Innate Immune Responses in the Pathogenesis of Baker's Asthma

Abstract

Background: S100A8 and S100A9 can be produced by lipopolysaccharide-stimulated granulocytes and provoke an innate immune-mediated airway inflammation. Involvement of S100A8 and S100A9 has been implicated in asthma. To further understand the role of S100A8 and S100A9 during innate immune responses in baker's asthma, we investigated the associations of serum S100A8 and S100A9 with exposure to bakery allergens and polymorphisms of the Toll-like receptor 4 (TLR4) gene. Methods: Totally, 381 bakery workers and 100 unexposed healthy controls were recruited. Skin prick tests for bakery allergens were performed. Serum levels of S100A8, S100A9, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, and interleukin (IL)-8 were measured using ELISA. Predictive values of serum S100A8 and S100A9 in bakery workers were evaluated by receiver-operating characteristic (ROC) curves. Polymorphisms of TLR4 -2027A→G and -1608T→C were genotyped. Results: Higher serum levels of S100A8 and S100A9 were noted in bakery workers compared to the normal controls (p < 0.001); however, no significant differences were noted according to work-related symptoms. The area under the ROC curve of serum S100A8 was 0.886 for occupational exposure (p < 0.001). The TLR4 -1608CC genotype was significantly associated with a higher serum S100A8 level (p = 0.025). Serum S100A8 and S100A9 levels were correlated with serum levels of MPO (r = 0.396 and 0.189, respectively), TNF-α (r = 0.536 and 0.280, respectively), and IL-8 (r = 0.540 and 0.205, respectively; p < 0.001 for all). Conclusion: S100A8 and S100A9 are involved in innate immune responses under the regulation of TLR4 polymorphisms in baker's asthma pathogenesis. Serum S100A8 could be a potential biomarker for predicting occupational exposure to wheat flour in bakery workers.

Decreased S100A9 Expression Promoted Rat Airway Smooth Muscle Cell Proliferation by Stimulating ROS Generation and Inhibiting p38 MAPK

“…In asthmatic patients, S100A9 expression was downregulated in sputum [21]. However, S100A9 level was elevated in serum of bakery workers and involved in innate immune responses of baker's asthma pathogenesis [22]. Our previous study showed that S100A9 is one of the differentially expressed genes in a rat lung model of asthma [23].…”

Calgranulin C (S100A12) Is Differentially Expressed in Subtypes of Chronic Rhinosinusitis

“…38 Calprotectin (S100A8) levels have been correlated with increased expression of interferon gamma, 39 whereas S100A9 enhances IL-1b secretion, which is abrogated by priming with Th2 cytokines. 40 Contrastingly, S100A8/A9 is upregulated in the lung and skin of respective patients with asthma 41 and chronic atopic dermatitis, both of these conditions are associated with Th2-type cytokines including IL-5, IL-13, and IL-4. 38 Our biochemical and IHC studies demonstrate that S100A12 and HNE are significantly increased in patients with CRSsNP compared to controls and that patients with CRSwNP had similar S100A12 levels to those of controls.…”

Eosinophils mediate SIgA production triggered by TLR2 and TLR4 to control Ascaris suum infection in mice

“…Proteomic evaluation of hepatic resistance to larval ascariasis revealed upregulation of genes related to innate and adaptive immune responses in Ascaris -infected mice [ 59 ]. These genes may act as markers of danger-associated molecular patterns (DAMPs) interacting with TLR4 like that observed in asthma [ 60 , 61 ]. Increased TLR2 and TLR4 expression in circulating B-cells during helminth infection has already been demonstrated, reflecting systemic exposure to the microbial ligands [ 62 ].…”